Search

The guppy Y chromosome has been considered a model system for the evolution of suppressed recombination between sex chromosomes, and it has been proposed that complete sex-linkage has evolved across about 3 Mb surrounding this fish's sex-determining locus, followed by recombination suppression across a further 7 Mb of the 23 Mb XY pair, forming younger "evolutionary strata". Sequences of the guppy genome show that Y is very similar to the X chromosome. Knowing which parts of the Y are completely nonrecombining, and whether there is indeed a large completely nonrecombining region, are important for understanding its evolution. Here, we describe analyses of PoolSeq data in samples from within multiple natural populations from Trinidad, yielding new results that support previous evidence for occasional recombination between the guppy Y and X. We detected recent demographic changes, notably that downstream populations have higher synonymous site diversity than upstream ones and other expected signals of bottlenecks. We detected evidence of associations between sequence variants and the sex-determining locus, rather than divergence under a complete lack of recombination. Although recombination is infrequent, it is frequent enough that associations with SNPs can suggest the region in which the sex-determining locus must be located. Diversity is elevated across a physically large region of the sex chromosome, conforming to predictions for a genome region with infrequent recombination that carries one or more sexually antagonistic polymorphisms. However, no consistently male-specific variants were found, supporting the suggestion that any completely sex-linked region may be very small.

Phytophthora root and stem rot is a major constraint to soybean [Glycine max (L.) Merr.] production worldwide. Deployment of single dominant Resistance to Phytophthora sojae (Rps) genes are an effective management strategy for this disease. However, due to increasing diversity in P. sojae populations for pathotype, new effective Rps genes are needed. Two recombinant inbred line (RIL) populations, each derived from a cross with Williams (susceptible) and resistant accessions PI 407974B and PI 424487B, were evaluated for resistance with one or more P. sojae pathotypes: OH1 (vir 7), OH4 (vir 1a, 1c, 7), OH7 (vir 1a, 3a, 3c, 4, 5, 6, 7), OH25 (vir 1a, 1b, 1c, 1k, 7), and 1.S.1.1 (1a, 1b, 1k, 2, 3a, 3c, 4, 5, 6, 7, 8). Molecular maps were assembled with BARCSoySNP6K BeadChip, simple-sequence repeat, and Kompetitive Allele Specific polymerase chain reaction markers. A total of three Rps loci were mapped, one near Rps1 on Chromosome 3 and two near Rps4/6 on chromosome 18. Quantitative trait loci and straight linkage maps confirmed the loci. Resistance to P. sojae pathotypes 1.S.1.1 and/or OH7 was mapped to Chromosome 3 in the PI 407974B RIL population. PI 407974B and PI 424487B RIL populations have Rps loci on chromosome 18 toward OH4 and OH25, respectively, which are near the Rps4/6 region. Although these PIs may have novel Rps genes/alleles and could assist in the deployment and pyramiding of resistance against P. sojae, care should be taken because these may condition defense reactions to some P. sojae pathotypes but not to all., Funding for this project was provided by the United Soybean Board, the Ohio Soybean Council, and the Ohio State University Center for Applied Plant Sciences, College of Food, Agricultural and Environmental Sciences, Center for Soybean Research. In addition, we wish to acknowledge support from the Molecular Cellular Imaging Center at Ohio Agricultural Research and Development Center. Salaries and research support for this project was provided by State and Federal Funds appropriated to the Ohio Agricultural Research and Development Center, The Ohio State University and the National Institute of Food and Agriculture, USDA, Hatch projects Development of Disease Management Strategies for Soybean Pathogens in Ohio OHO01303 and Genetic Analysis of Soybean Added-Value Traits and Soybean Variety Development for Ohio OHO01279.

Here, we present an annotated, chromosome-anchored, genome assembly for Lake Trout (Salvelinus namaycush) - a highly diverse salmonid species of notable conservation concern and an excellent model for research on adaptation and speciation. We leveraged Pacific Biosciences long-read sequencing, paired-end Illumina sequencing, proximity ligation (Hi-C) sequencing, and a previously published linkage map to produce a highly contiguous assembly composed of 7378 contigs (contig N50 = 1.8 Mb) assigned to 4120 scaffolds (scaffold N50 = 44.975 Mb). Long read sequencing data were generated using DNA from a female double haploid individual. 84.7% of the genome was assigned to 42 chromosome-sized scaffolds and 93.2% of Benchmarking Universal Single Copy Orthologues were recovered, putting this assembly on par with the best currently available salmonid genomes. Estimates of genome size based on k-mer frequency analysis were highly similar to the total size of the finished genome, suggesting that the entirety of the genome was recovered. A mitochondrial genome assembly was also produced. Self-versus-self synteny analysis allowed us to identify homeologs resulting from the salmonid specific autotetraploid event (Ss4R) as well as regions exhibiting delayed rediploidization. Alignment with three other salmonid genomes and the Northern Pike (Esox lucius) genome also allowed us to identify homologous chromosomes in related taxa. We also generated multiple resources useful for future genomic research on Lake Trout, including a repeat library and a sex-averaged recombination map. A novel RNA sequencing data set for liver tissue was also generated in order to produce a publicly available set of annotations for 49,668 genes and pseudogenes. Potential applications of these resources to population genetics and the conservation of native populations are discussed.

The contemporary effective population size Ne is important in many disciplines including population genetics, conservation science and pest management. One of the most popular methods of estimating this quantity uses temporal changes in allele frequency due to genetic drift. A significant assumption of the existing methods is the independence among loci while constructing confidence intervals (CI), which restricts the types of species or genetic data applicable to the methods. Although genetic linkage does not bias point Ne estimates, applying these methods to linked loci can yield unreliable CI that are far too narrow. We extend the current methods to enable the use of many linked loci to produce precise contemporary Ne estimates, while preserving the targeted CI width and coverage. This is achieved by deriving the covariance of changes in allele frequency at linked loci in the face of recombination and sampling errors, such that the extra sampling variance due to between-locus correlation is properly handled. Extensive simulations are used to verify the new method. We apply the method to two temporally spaced genomic data sets of Anopheles mosquitoes collected from a cluster of villages in Burkina Faso between 2012 and 2014. With over 33,000 linked loci considered, the Ne estimate for Anopheles coluzzii is 9,242 (95% CI 5,702-24,282), and for Anopheles gambiae it is 4,826 (95% CI 3,602-7,353).

For the past two to three decades, forensic DNA evidence has been analyzed with a limited number of short tandem repeats (STRs), and these STRs are usually assumed to be independent for statistical calculations. With the development and implementation of the MPS technologies, more autosomal markers, both single nucleotide polymorphisms (SNPs) and STRs, can be analyzed. A number of these markers are physically very close to each other, and it may not be appropriate to assume all these markers are genetically unlinked or in linkage equilibrium. In this study, publicly accessible genomic data from five representative populations were used to evaluate the genetic linkage and linkage disequilibrium (LD) between autosomal markers represented in six major commercial panels (in total, 362 markers). Among the 3041 syntenic marker pairs, 1524 pairs had sex-average genetic distances

Background Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting apocrine gland-bearing skin in the axilla, groin and under the breasts. Mutations of the gamma secretase gene complex, which is essential in the activation of Notch signalling pathways, were shown in some families with HS and in a few sporadic cases. Although an imbalance in Notch signalling is implicated in the pathogenesis, the exact mechanism of HS development is yet unknown. Objectives We aim to investigate the genetic basis of HS by determining the presence of mutations of gamma secretase gene complex in a cohort of HS patients and by searching for a disease-causing pathogenic variant in a multi-generational HS family using parametric linkage analysis. Methods Thirty-eight patients clinically diagnosed with HS were included in this study. All exons and exon-intron boundaries of the genes encoding gamma secretase complex consisting of six genes: APH1A, APH1B, PSENEN, NCSTN, PSEN1 and PSEN2 were sequenced by Sanger technique. Genetic mapping with parametric linkage analysis for the patients in the family was performed with eight affected and four healthy individuals. The logarithm of odds was calculated. Results In a sporadic patient with early-onset, severe lesions in axilla and groin, a novel single-nucleotide deletion causing frameshift in exon 1 of the NCSTN gene was identified ((NM_015331.3): c.38delG, p.(Gly13Glufs*15)). The LOD score of 1.5 was never exceeded in any region of the genome, pointing towards intricate multi-genic inheritance pattern within the affected family. Conclusions The gamma secretase gene complex mutations were rare in our cohort (3.2%). Besides, our analysis indicates a possible complex multi-genic inheritance in a seemingly autosomal dominantly inherited large HS family. Genetics of both familial and sporadic HS may be complicated in most cases, and the role of other potential genes such as autoinflammatory and modifier genes as well as environmental factors may influence the pathogenesis.

Chinese perch, Siniperca chuatsi (Basilewsky), is one of the most commercially important cultured fishes in China. In the present study, a high-density genetic linkage map of Chinese perch was constructed by genotyping-by-sequencing technique with an F1 mapping panel containing 190 progenies. A total of 2328 SNPs were assigned to 24 linkage groups (LGs), agreeing with the chromosome haploid number in this species (n = 24). The sex-averaged map covered 97.9% of the Chinese perch genome, with the length of 1694.3 cM and a marker density of 0.7 cM/locus. The number of markers per LG ranged from 57 to 222, with a mean of 97. The length of LGs varied from 43.2 to 108.2 cM, with a mean size of 70.6 cM. The recombination rate of females was 1.5:1, which was higher than that of males. To better understand the distribution pattern of segregation distortion between the two sexes of Chinese perch, the skewed markers were retained and used to reconstruct the sex-specific maps. The 16 segregation distortion regions were identified on 10 LGs of the female map, while 12 segregation distortion regions on eight LGs of the male map. Among these LGs, six LGs matched between the sex-specific maps. This high-density linkage map could provide a solid basis for identifying QTL associated with economically important traits, and for implementing marker-assisted selection breeding of Chinese perch.

A chromosome-specific painting technique has been developed which combines the most recent approaches of the companion disciplines of molecular cytogenetics and genome research. We developed seven oligonucleotide (oligo) pools derivd from single-copy sequences on chromosomes 1 to 7 of barley (Hordeum vulgare L.) and corresponding collinear regions of wheat (Triticum aestivum L.). The seven groups of pooled oligos comprised between 10 986 and 12 496 45-bp monomers, and these then produced stable fluorescence in situ hybridization (FISH) signals on chromosomes of each linkage group of wheat and barley. The pooled oligo probes were applied to high-throughput karyotyping of the chromosomes of other Triticeae species in the genera Secale, Aegilops, Thinopyrum, and Dasypyrum, and the study also extended to some wheat-alien amphiploids and derived lines. We demonstrated that a complete set of whole-chromosome oligo painting probes facilitated the study of inter-species chromosome homologous relationships and visualized non-homologous chromosomal rearrangements in Triticeae species and some wheat-alien species derivatives. When combined with other non-denaturing FISH procedures using tandem-repeat oligos, the newly developed oligo painting techniques provide an efficient tool for the study of chromosome structure, organization, and evolution among any wild Triticeae species with non-sequenced genomes.

Article publié dans la revue Evolution doi: 10.1111/evo.14129. Voir hal-03375711.; International audience; The evolution of mate preferences may depend on natural selection acting on the mating cues and on the underlying genetic architecture. While the evolution of assortative mating with respect to locally adapted traits has been well-characterized, the evolution of disassortative mating is poorly characterized. Here we aim at understanding the evolution of disassortative mating for traits under strong balancing selection, by focusing on polymorphic mimicry as an illustrative example. Positive frequency-dependent selection exerted by predators generates local selection on wing patterns acting against rare variants and promoting local monomorphism. This acts across species boundaries, favouring Mullerian mimicry among defended species. In this well-characterized adaptive landscape, polymorphic mimicry is rare but is observed in a butterfly species, associated with polymorphic chromosomal inversions. Because inversions are often associated with recessive deleterious mutations, we hypothesize they may induce heterozygote advantage at the color pattern locus, putatively favoring the evolution of disassortative mating. To explore the conditions underlying the emergence of disassortative mating, we modeled both a trait locus (colour pattern for instance), subject to mutational load, and a preference locus. We confirm that heterozygote advantage favors the evolution of disassortative mating and show that disassortative mating is more likely to emerge if at least one allele at the trait locus is free from any recessive deleterious mutations. We modelled different possible genetic architectures underlying mate choice behaviour, such as self referencing alleles, or specific preference or rejection alleles. Our results showed that self referencing or rejection alleles linked to the color pattern locus can be under positive selection and enable the emergence of disassortative mating. However rejection alleles allow the emergence of disassortative mating only when the color pattern and preference loci are tightly linked. Our results therefore provide relevant predictions on both the selection regimes and the genetic architecture favoring the emergence of disassortative mating and a theoretical framework in which to interprete empirical data on mate preferences in wild populations.

Blast disease, caused by the Magnaporthe oryzae Triticum pathotype (MoT), is a major concern for wheat production in tropical and subtropical regions. The most destructive symptoms occur in wheat spikes. Infected spikes become bleached due to partial or total sterility, producing small and wrinkled grains. High disease pressure of the disease results in significant yield losses. This study aimed to identify wheat quantitative trait loci (QTLs) conferring resistance to blast disease at the heading stage. A doubledhaploid population was developed from the cross between BRS 209 (susceptible) and CBFusarium ENT014 (resistant, carrying the 2NS translocation). A linkage map was constructed containing 5,381 molecular markers and the inclusive composite interval mapping method was employed for QTL detection. Four QTLs were mapped in response to two MoT isolates. The major QTL identified on the 2AS chromosome explained an average of 84.0% of the phenotypic variation for spike bleaching at 9 days postinoculation and reinforces the potency of the 2NS translocation. Recombination between the distal region of chromosome 2AS and the 2NS marker was found. These results could explain why some lines carrying the VENTRIUP/LN2 marker have a variable reaction to the disease. QTLs on 5B and 7B chromosomes were also identified. Two mechanisms of resistance were hypothesized: the hypersensitive response and resistance to colonization of host tissues. The KASP markers thus developed and simple sequence repeats (SSRs) allocated in QTL regions can be used in the future for the development of wheat blast-resistant cultivars. KEYWORDS 2NS/2AS translocation, brusone, doubled-haploid population, Magnaporthe oryzae Triticum pathotype, major QTL, Triticum aestivum

"Magic traits," in which the same trait is both under divergent ecological selection and forms the basis of assortative mating, have been sought after due to their supposed unique ability to promote divergence with gene flow. Here, we ask how unique magic traits are, by exploring whether a tightly linked complex of a locus under divergent selection and a locus that acts as a mating cue can mimic a magic trait in its divergence. We find that these "pseudomagic traits" can be very effective in promoting divergence; with tight linkage they are essentially as effective as a magic trait and with loose linkage, and even no linkage, divergence can still be enhanced. Distinguishing between magic and pseudomagic traits in empirical cases may thus not be important when inferring their role in divergence. The ability of divergence in the mating trait to drive divergence in the ecological trait by lowering the effective migration rate, which occurs somewhat even without linkage, is particularly striking; magic traits are typically considered to have the other direction of causality. Our results thus suggest that divergence in a mating trait can at least modestly increase local adaption by allowing more ecological divergence, particularly with tighter linkage.

Meiotic recombination rates vary considerably between species, populations and individuals. The genetic exchange between homologous chromosomes plays a major role in evolution by breaking linkage between advantageous and deleterious alleles in the case of introgressions. Identifying recombination rate modifiers is thus of both fundamental and practical interest to understand and utilize variation in meiotic recombination rates. We investigated recombination rate variation in a large intraspecific hybrid population (named HEB-25) derived from a cross between domesticated barley and 25 wild barley accessions. We observed quantitative variation in total crossover number with a maximum of a 1.4-fold difference between subpopulations and increased recombination rates across pericentromeric regions. The meiosis-specific α-kleisin cohesin subunit REC8 was identified as a candidate gene influencing crossover number and patterning. Furthermore, we quantified wild barley introgression patterns and revealed how local and genome-wide recombination rate variation shapes patterns of introgression. The identification of allelic variation in REC8 in combination with the observed changes in crossover patterning suggest a difference in how chromatin loops are tethered to the chromosome axis, resulting in reduced crossover suppression across pericentromeric regions. Local and genome-wide recombination rate variation is shaping patterns of introgressions and thereby directly influences the consequences of linkage drag.

The role of genetic architecture in adaptation to novel environments has received considerable attention when the source of adaptation variation isde novomutation. Relatively less is known when the source of adaptive variation is inter- or intraspecific hybridization. We model hybridization between divergent source populations and subsequent colonization of an unoccupied novel environment using individual-based simulations in order to understand the influence of genetic architecture on the timing of colonization and the mode of adaptation. We find that two distinct categories of genetic architecture facilitate rapid colonization but that they do so in qualitatively different ways. For few and/or tightly linked loci, the mode of adaptation is via the recovery of adaptive parental genotypes. With many unlinked loci, the mode of adaptation is via the generation of novel hybrid genotypes. The first category results in the shortest colonization lag phases across the widest range of parameter space, but further adaptation is mutation limited. The second category takes longer and is more sensitive to genetic variance and dispersal rate, but can facilitate adaptation to environmental conditions which exceed the tolerance of parental populations. These findings have implications for understanding the origins of biological invasions and the success of hybrid populations.

Our aim is to describe a family with a nonsyndromic form of hereditary gingival fibromatosis (HGF) and discuss genetic characteristics of this rare disease by reviewing reported cases. A mother and three descendants were diagnosed with HGF. There was marked variable expressivity: from severe generalized gingival overgrowth in a 16-year-old boy (the proband) to minimal manifestations in the mother. The proband was submitted to gingivectomy and gingivoplasty. In younger siblings, the disease remained stable for 5 years, suggesting that clinical surveillance is a good option. The diagnosis was supported by histopathological examination. Analysis of this family and literature-reported cases supports that HGF most frequently shows an autosomal dominant inheritance with high penetrance and variable expressivity. Neomutations and gonadal mosaicism do not seem to be a rare event. Although five loci have been mapped by linkage analysis, only two genes, SOS1 and REST, were identified in four families.

Nonsyndromic hearing loss is an extremely heterogeneous disorder. Thus, clinical diagnostics is challenging, in particular due to differences in the etiology of hearing loss between populations. With this study, we wanted to elucidate the genetic basis of hearing loss in 61 consanguineous Egyptian families. In 25 families, linkage analysis was used as a prescreening to identify regions for targeted sequencing of candidate genes. Initially, the coding regions of 12 and later of 94 genes associated with hearing loss were enriched and subjected to massively parallel sequencing (MPS) with diagnostic yields of 36% and 75%, respectively. Causative variants were identified in 48 families (79%). They were found in 23 different genes with the majority being located in MYO15A (15.3%), SLC26A4 (9.7%), GJB2 (8.3%), and MYO7A (6.4%). As many as 32 variants were novel ones at the time of detection. Five variants were shared by two, three, or even four families. Our study provides a first survey of the mutational spectrum of deaf patients in Egypt revealing less GJB2 variants than in many European populations. It underlines the value of targeted enrichment of well-selected deafness genes in combination with MPS in the diagnostics of this frequent and genetically heterogeneous disorder.

Many root‐knot nematode (RKN) species (Meloidogyne spp.) are polyphagous and cultivated tomato (Solanum lycopersicum) is one of their preferential hosts, leading to significant losses. It is known that the dominant Mi‐1.2 gene in tomato confers resistance to the three most important RKN species—M. incognita, M. javanica, and M. arenaria, and minor species—M. ethiopica, M. hispanica, and M. luci. However, little information is available about resistance of tomatoes carrying this gene to other tomato‐infecting RKN species. In this study, resistance conferred by the Mi‐1.2 gene/locus was evaluated against populations of 15 Meloidogyne species, employing tomato cultivars Santa Clara (homozygous recessive mi‐1.2/mi‐1.2, susceptible) and Debora Plus (heterozygous Mi‐1.2/mi‐1.2, resistant). Debora Plus was susceptible only to M. enterolobii and M. hapla, and was resistant to the other Brazilian populations of M. arenaria, M. ethiopica, M. exigua, M. hispanica, M. incognita, M. inornata, M. izalcoensis M. javanica, M. konaensis, M. luci, M. morocciensis, M. paranaensis, and M. petuniae. Mi‐1.2 is located on tomato chromosome 6 within a cluster of seven homologous genes of the nucleotide‐binding site leucine‐rich repeat (NBS‐LRR) family; further research is required to confirm if this multiple Meloidogyne spp. resistance phenotype is controlled exclusively by Mi‐1.2 or by combined action of other closely linked genes. This evaluation of resistance of the Debora Plus cultivar to several Meloidogyne species suggests that the Mi‐1.2 gene/locus may reduce losses induced by a wide range of Meloidogyne spp. Further studies using additional resistant cultivars and other populations of Meloidogyne spp. are needed to confirm these results.

Next generation sequencing technologies have made it possible to investigate the role of rare variants (RVs) in disease etiology. Because RVs associated with disease susceptibility tend to be enriched in families with affected individuals, study designs based on affected sib pairs (ASP) can be more powerful than case–control studies. We construct tests of RV‐set association in ASPs for single genomic regions as well as for multiple regions. Single‐region tests can efficiently detect a gene region harboring susceptibility variants, while multiple‐region extensions are meant to capture signals dispersed across a biological pathway, potentially as a result of locus heterogeneity. Within ascertained ASPs, the test statistics contrast the frequencies of duplicate rare alleles (usually appearing on a shared haplotype) against frequencies of a single rare allele copy (appearing on a nonshared haplotype); we call these allelic parity tests. Incorporation of minor allele frequency estimates from reference populations can markedly improve test efficiency. Under various genetic penetrance models, application of the tests in simulated ASP data sets demonstrates good type I error properties as well as power gains over approaches that regress ASP rare allele counts on sharing state, especially in small samples. We discuss robustness of the allelic parity methods to the presence of genetic linkage, misspecification of reference population allele frequencies, sequencing error and de novo mutations, and population stratification. As proof of principle, we apply single‐ and multiple‐region tests in a motivating study data set consisting of whole exome sequencing of sisters ascertained with early onset breast cancer.

COX15 mutations were shown to underlie Leigh syndrome (LS), a progressive subacute necrotizing encephalopathy caused by defects in the mitochondrial respiratory chain. Here, two siblings of consanguineous kindred presented in infancy with a syndrome of hypotonia, nystagmus, psychomotor retardation, and pyramidal signs. Toward the end of their second year, both patients developed progressive quadriparesis, convulsions, and pseudobulbar palsy. Similar to two previously reported cases, one of the two affected siblings had severe hypertrophic obstructive cardiomyopathy, hearing loss, and no visual response. Through linkage analysis and whole-exome sequencing, we identified a homozygous p.R217W mutation in Cytochrome C oxidase assembly protein COX15 homolog. Consistent with the known heterogeneity of mitochondrial diseases in general and that of LS in particular, several phenotypic features were markedly distinguished between the affected siblings and in relation to previous reports of COX15 mutations. Interestingly, of the previously reported five cases of COX15-mutated patients, all of different ethnic origins, three had a p.R217W mutation. We highlight p.R217W as a hotspot mutation in COX15 and delineate the phenotypic variability, both between the patients we describe and in all cases reported to date.

Introduction Essential tremor (ET) is one of the most prevalent movement disorders. The genetic etiology of ET has not been well defined although a significant proportion (≥50%) are familial cases. Linkage analysis and genome‐wide association studies (GWASs) have identified several risk variants. In recent years, whole‐exome sequencing of ET has revealed several specific causal variants in FUS (p.Q290X), HTRA2 (p.G399S), and TENM4 (c.4324 G>A, c.4100C>A, and c.3412G>A) genes. Objective To investigate the genetic contribution of these three genes to ET, the protein‐coding sequences of FUS, HTRA2, and TENM4 were analyzed in a total of 238 ET patients and 272 controls from eastern China using direct Sanger sequencing. Results We identified two synonymous coding single nucleotide polymorphisms (SNPs), rs741810 and rs1052352 in FUS, and three previously reported synonymous SNPs, rs11237621, rs689369, and rs2277277 in TENM4. No nonsynonymous exonic variants were identified in these subjects. We found that the frequency of the rs1052352C allele was significantly higher (P = .001) in the ET group than in the control group. Conclusion Overall, our findings suggest that rs1052352 of FUS might contribute to ET risk in Chinese population.

Mouse dorsal coat hair types, guard, awl, auchene and zigzag, develop in three consecutive waves. To date, it is unclear if these hair types are determined genetically through expression of specific factors or can change based on their mesenchymal environment. We undertook a novel approach to this question by studying individual hair type in 67 Collaborative Cross (CC) mouse lines and found significant variation in the proportion of each type between strains. Variation in the proportion of zigzag, awl and auchene, but not guard hair, was largely due to germline genetic variation. We utilised this variation to map a quantitative trait locus (QTL) on chromosome 12 that appears to influence a decision point switch controlling the propensity for either second (awl and auchene) or third wave (zigzag) hairs to develop. This locus contains two strong candidates, Sostdc1 and Twist1, each of which carry several ENCODE regulatory variants, specific to the causal allele, that can influence gene expression, are expressed in the developing hair follicle, and have been previously reported to be involved in regulating human and murine hair behaviour, but not hair subtype determination. Both of these genes are likely to play a part in hair type determination via regulation of BMP and/or WNT signalling.

Chromosomal substitution strategies provide a powerful tool to anonymously reveal the relationship between DNA sequence variants and a normal or disease phenotype of interest. Even in this age of CRISPR-Cas9 genome engineering, the knockdown or overexpression of a gene provides relevant information to our understanding of complex disease only when a close association of an allelic variant with the phenotype has first been established. Limitations of genetic linkage approaches led to the development of more efficient breeding strategies to substitute chromosomal segments from one animal strain into the genetic background of a different strain, enabling a direct comparison of the phenotypes of the strains with variant(s) that differ only at a defined locus. This substitution can be a whole chromosome (consomic), a part of a chromosome (congenic), or as small as only a single or several alleles (subcongenics). In contrast to complete knockout of a specific candidate gene of interest, which simply studies the effects of complete elimination of the gene, the substitution of naturally occurring variants can provide special insights into the functional actions of wild-type alleles. Strategies for production of these inbred strains are reviewed, and a number of examples are used to illustrate the utility of these model systems. Consomic/congenic strains provide a number of experimental advantages in the study of functions of genes and their variants, which are emphasized in this article, such as replication of experimental studies; determination of temporal relationships throughout a life; rigorously controlled experiments in which relations between genotype and phenotype can be tested with the confounding effects of heterogeneous genetic backgrounds, both targeted and multilayered; and "omic" studies performed at many levels of functionality, from molecules to organelles, cells to organs, and organs to organismal behavior across the life span. The application of chromosomal substitution strategies and development of consomic/congenic rat and mouse strains have greatly expanded our knowledge of genomic variants and their phenotypic relationship to physiological functions and to complex diseases such as hypertension and cancer. © 2020 American Physiological Society. Compr Physiol 10:365-388, 2020.

The rapid development and application of molecular marker assays have facilitated genomic selection and genome-wide linkage and association studies in wheat breeding. Although PCR-based markers (e.g. simple sequence repeats and functional markers) and genotyping by sequencing have contributed greatly to gene discovery and marker-assisted selection, the release of a more accurate and complete bread wheat reference genome has resulted in the design of single-nucleotide polymorphism (SNP) arrays based on different densities or application targets. Here, we evaluated seven types of wheat SNP arrays in terms of their SNP number, distribution, density, associated genes, heterozygosity and application. The results suggested that the Wheat 660K SNP array contained the highest percentage (99.05%) of genome-specific SNPs with reliable physical positions. SNP density analysis indicated that the SNPs were almost evenly distributed across the whole genome. In addition, 229 266 SNPs in the Wheat 660K SNP array were located in 66 834 annotated gene or promoter intervals. The annotated genes revealed by the Wheat 660K SNP array almost covered all genes revealed by the Wheat 35K (97.44%), 55K (99.73%), 90K (86.9%) and 820K (85.3%) SNP arrays. Therefore, the Wheat 660K SNP array could act as a substitute for other 6 arrays and shows promise for a wide range of possible applications. In summary, the Wheat 660K SNP array is reliable and cost-effective and may be the best choice for targeted genotyping and marker-assisted selection in wheat genetic improvement.

Summary Ficus erecta, a wild relative of the common fig (F. carica), is a donor of Ceratocystis canker resistance in fig breeding programmes. Interspecific hybridization followed by recurrent backcrossing is an effective method to transfer the resistance trait from wild to cultivated fig. However, this process is time consuming and labour intensive for trees, especially for gynodioecious plants such as fig. In this study, genome resources were developed for F. erecta to facilitate fig breeding programmes. The genome sequence of F. erecta was determined using single‐molecule real‐time sequencing technology. The resultant assembly spanned 331.6 Mb with 538 contigs and an N50 length of 1.9 Mb, from which 51 806 high‐confidence genes were predicted. Pseudomolecule sequences corresponding to the chromosomes of F. erecta were established with a genetic map based on single nucleotide polymorphisms from double‐digest restriction‐site‐associated DNA sequencing. Subsequent linkage analysis and whole‐genome resequencing identified a candidate gene for the Ceratocystis canker resistance trait. Genome‐wide genotyping analysis enabled the selection of female lines that possessed resistance and effective elimination of the donor genome from the progeny. The genome resources provided in this study will accelerate and enhance disease‐resistance breeding programmes in fig., Significance Statement We report the genome sequence of Ficus erecta, which is a donor of Ceratocystis canker resistance in breeding programmes in common fig (F. carica). Using the genome information, we identified a candidate gene for resistance and developed a DNA marker that was tightly linked to the trait. The genome resources provided in this study will accelerate and enhance disease‐resistance breeding programmes in fig.

Salt stress is an ever‐present threat to rice production worldwide. Rice salinity tolerance is complex, both genetically and physiologically. The success and effectiveness in selecting salt‐tolerant rice variety require the identification of QTL for the tolerance and closely linked molecular markers. In the present study, a RIL population consisting of 148 lines, derived from a cross between IR29 (salt‐sensitive) and Pokkali (salt‐tolerant), was used to identify new QTL for salt tolerance and investigate the relationships between salt stress caused injury and the changes in different physiological and morphological traits at the seedling stage. 14,470 high‐quality SNP markers generated by the Rice 56K SNP array were converted to 1,467 bin markers for linkage mapping. A high‐density genetic linkage map covering 1,680.9 cM was constructed, with the physical to genetic distance ratio being 222 Kb/cM. In total, 23 QTL for different salt tolerance indices were identified, including the previously reported Saltol which is currently used in breeding programmes. Three QTL for salt injury score (SIS) were located on chromosomes 1, 4 and 12, all being closely related to the long‐distant Na+ transport from roots to shoots. These QTL showed additive effects, thus can be effectively used in breeding programme to pyramid various tolerance genes.

The superb fairy-wren, Malurus cyaneus, is one of the most iconic Australian passerine species. This species belongs to an endemic Australasian clade, Meliphagides, which diversified early in the evolution of the oscine passerines. Today, the oscine passerines comprise almost half of all avian species diversity. Despite the rapid increase of available bird genome assemblies, this part of the avian tree has not yet been represented by a high-quality reference. To rectify that, we present the first high-quality genome assembly of a Meliphagides representative: the superb fairy-wren. We combined Illumina shotgun and mate-pair sequences, PacBio long-reads, and a genetic linkage map from an intensively sampled pedigree of a wild population to generate this genome assembly. Of the final assembled 1.07-Gb genome, 975 Mb (90.4%) was anchored onto 25 pseudochromosomes resulting in a final superscaffold N50 of 68.11 Mb. This high-quality bird genome assembly is one of only a handful which is also accompanied by a genetic map and recombination landscape. In comparison to other pedigree-based bird genetic maps, we find that the fairy-wren genetic map more closely resembles those of Taeniopygia guttata and Parus major maps, unlike the Ficedula albicollis map which more closely resembles that of Gallus gallus. Lastly, we also provide a predictive gene and repeat annotation of the genome assembly. This new high-quality, annotated genome assembly will be an invaluable resource not only regarding the superb fairy-wren species and relatives but also broadly across the avian tree by providing a novel reference point for comparative genomic analyses.

Hearing loss (HL) is the most common sensory disorder worldwide and genetic factors contribute to approximately half of congenital HL cases. HL is subject to extensive genetic heterogeneity, rendering molecular diagnosis difficult. Mutations of the transmembrane channel-like 1 (TMC1) gene cause hearing defects in humans and mice. The precise function of TMC1 protein in the inner ear is unknown, although it is predicted to be involved in functional maturation of cochlear hair cells. TMC1 mutations result in autosomal recessive (DFNB7/11) and sometimes dominant (DFNA36) nonsyndromic HL. Mutations in TMC1 are responsible for a significant portion of HL, particularly in consanguineous populations. To evaluate the importance of TMC1 mutations in the Saudi population, we used a combination of autozygome-guided candidate gene mutation analysis and targeted next generation sequencing in 366 families with HL previously shown to lack mutations in GJB2. We identified 12 families that carried five causative TMC1 mutations; including three novel (c.362+3A > G; c.758C > T [p.Ser253Phe]; c.1396_1398delACC [p.Asn466del]) and two reported mutations (c.100C > T [p.Arg34Ter]; c.1714G > A [p.Asp572Asn]). Each of the identified recessive mutation was classified as severe, by both age of onset and severity of HL. Similarly, consistent with the previously reported dominant variant p.Asp572Asn, the HL phenotype was progressive. Eight families in our cohort were found to share the pathogenic p.Arg34Ter mutation and linkage disequilibrium was observed between p.Arg34Ter and SNPs investigated. Our results indicate that TMC1 mutations account for about 3.3% (12/366) of Saudi HL cases and that the recurrent TMC1 mutation p.Arg34Ter is likely to be a founder mutation.

Vitiligo is an autoimmune disease in which destruction of skin melanocytes results in patches of white skin and hair. Genome-wide linkage studies and genome-wide association studies in European ancestry cases identified over 50 vitiligo susceptibility loci, defining a model of melanocyte-directed autoimmunity. Vitiligo heritability is exceedingly high, ~2/3 coming from common and ~1/3 from rare genomic variants; ~20% of vitiligo risk is environmental. Vitiligo genetic risk is polygenic, with greater additive risk in multiplex vitiligo families than simplex cases. Vitiligo age-of-onset is bimodal, also involving a major genetic component; a MHC enhancer haplotype confers extreme risk for vitiligo (OR 8.1) and early disease onset, increasing expression of HLA-DQB1 mRNA and HLA-DQ protein and thus perhaps facilitating presentation of triggering antigens. Vitiligo triggering also involves a major environmental component; dramatic delay in vitiligo age-of-onset, especially from 1973 to 2004, suggests that exposure or response to a key vitiligo environmental trigger diminished during this period. Together, these findings provide deep understanding of vitiligo pathogenesis and genetic architecture, suggesting that vitiligo represents a tractable model for investigating complex disease genetic architecture and predictive aspects of personalized medicine.

The leaf angle (LA), plant height (PH), and ear height (EH) are key plant architectural traits influencing maize (Zea mays L.) yield. However, their genetic determinants have not yet been well-characterized. Here, we developed a maize advanced backcross-nested association mapping population in Henan Agricultural University (HNAU-NAM1) comprised of 1,625 BC1 F4 /BC2 F4 lines. These were obtained by crossing a diverse set of 12 representative inbred lines with the common GEMS41 line, which were then genotyped using the MaizeSNP9.4K array. Genetic diversity and phenotypic distribution analyses showed considerable levels of genetic variation. We obtained 18-88 quantitative trait loci (QTLs) associated with LA, PH, and EH by using three complementary mapping methods, named as separate linkage mapping, joint linkage mapping, and genome-wide association studies. Our analyses enabled the identification of ten QTL hot-spot regions associated with the three traits, which were distributed on nine different chromosomes. We further selected 13 major QTLs that were simultaneously detected by three methods and deduced the candidate genes, of which eight were not reported before. The newly constructed HNAU-NAM1 population in this study will further broaden our insights into understanding of genetic regulation of plant architecture, thus will help to improve maize yield and provide an invaluable resource for maize functional genomics and breeding research.

Novel resistance sources to the pathogen Puccinia striiformis f. sp. tritici, which causes yellow rust (stripe rust), a widespread devastating foliar disease in wheat (Triticum aestivum L.), are in demand. Here, we tested two doubled haploid (DH) spring wheat populations derived from the genetic resources for resistance to yellow rust in field trials in Germany and Egypt. Additionally, we performed tests for all‐stage resistance (seedling resistance). We performed linkage mapping based on 15k Infinium SNP chip genotyping data that resulted in 3,567 and 3,457 polymorphic markers for DH Population 1 (103 genotypes) and DH Population 2 (148 genotypes), respectively. In DH Population 1, we identified a major and consistent quantitative trait locus (QTL) on chromosome 1B that explained up to 28 and 39% of the phenotypic variation in the field and seedling tests, respectively. The favorable allele was contributed by the line ‘TRI‐5645’, a landrace from Iran, and is most probably the yellow rust resistance (Yr) gene Yr10. In DH Population 2, the favorable allele of a major QTL on chromosome 6B was contributed by the line ‘TRI‐5310’, representing the variety ‘Eureke’ from France. This QTL was mainly effective in the German environments and explained up to 36% of the phenotypic variation. In Egypt, however, only a moderate resistance QTL was identified in the field tests and no resistance QTL was observed in the seedling tests. Our results demonstrate the usefulness of genetic resources to identify novel sources of resistance to yellow rust, including the “Warrior” race PstS10.

The continued success of lentil (Lens culinaris Medik.) genetic improvement relies on the availability of broad genetic diversity and new alleles need to be identified and incorporated into the cultivated gene pool. Availability of robust and predictive markers greatly enhances the precise transfer of genomic regions from unadapted germplasm. Quantitative trait loci (QTLs) for key phenological traits in lentil were located using a recombinant inbreed line (RIL) population derived from a cross between an Ethiopian landrace (ILL 1704) and a northern temperate cultivar (CDC Robin). Field experiments were conducted at Sutherland research farm in Saskatoon and at Rosthern, Saskatchewan, Canada during 2018 and 2019. A linkage map was constructed using 21,634 SNPs located on seven linkage groups (LGs) which correspond to the seven haploid chromosomes of lentil. Eight QTL were identified for six phenological traits. Flowering related QTL were identified at two regions on LG6. FLOWERING LOCUS T (FT) genes were annotated within the flowering time QTL interval based on the lentil reference genome. Similarly, a major QTL for post-flowering developmental processes was located on LG5 with several senescence-associated genes annotated within the QTL interval. The flowering time QTL was validated in a different genetic background indicating the potential use of the identified markers for marker-assisted selection to precisely transfer genomic regions from exotic germplasm into elite crop cultivars without disrupting adaptation.Core IdeasStable QTL were located for key phenological traits in lentil that lead to regional adaptation.FT genes are candidates for controlling flowering time in lentil grown in temperate environments.A major locus controlling post-flowering developmental processes was located on lentil LG5 with several senescence-associated genes annotated within the QTL interval.Markers identified in this study can be useful for marker-assisted selection to precisely transfer genomic regions from exotic germplasm into elite lentil cultivars without disrupting adaptation.

Anthracnose, caused byColletotrichum lentis, is a devastating disease of lentil (Lens culinaris Medik.) in western Canada. Growing resistant lentil cultivars is the most cost‐effective and environmentally friendly approach to prevent seed yield losses that can exceed 70%. To identify loci conferring resistance to anthracnose race 1 in lentil, biparental quantitative trait loci (QTL) mapping of two recombinant inbred line (RIL) populations was integrated with a genome‐wide association study (GWAS) using 200 diverse lentil accessions from a lentil diversity panel. A major‐effect QTL (qAnt1.Lc‐3) conferring resistance to race 1 was mapped to lentil chromosome 3 and colocated on the lentil physical map for both RIL populations. Clusters of candidate nucleotide‐binding leucine‐rich repeat (NB‐LRR) and other defense‐related genes were uncovered within the QTL region. A GWAS detected 14 significant single nucleotide polymorphism (SNP) markers associated with race 1 resistance on chromosomes 3, 4, 5, and 6. The most significant GWAS SNPs on chromosome 3 supported qAnt1.Lc‐3 and delineated a region of 1.6 Mb containing candidate resistance genes. The identified SNP markers can be directly applied in marker‐assisted selection (MAS) to accelerate the introgression of race 1 resistance in lentil breeding.

Recently, genome‐editing technology like clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 has improved the translational gap in the treatments mediated through gene therapy. The advantages of the CRISPR system, such as, work in the living cells and tissues, candidate this technique for the employing in experiments and the therapy of central nervous system diseases. Parkinson's disease (PD) is a widespread, disabling, neurodegenerative disease induced by dopaminergic neuron loss and linked to progressive motor impairment. Pathophysiological basis knowledge of PD has modified the PD classification model and expresses in the sporadic and familial types. Analyses of the earliest genetic linkage have shown in PD the inclusion of synuclein alpha (SNCA) genomic duplication and SNCA mutations in the familial types of PD pathogenesis. This review analyzes the structure, development, and function in genome editing regulated through the CRISPR/Cas9. Also, it explains the genes associated with PD pathogenesis and the appropriate modifications to favor PD. This study follows the direction by understanding the PD linking analyses in which the CRISPR technique is applied. Finally, this study explains the limitations and future trends of CRISPR service in relation to the genome‐editing process in PD patients' induced pluripotent stem cells., Parkinson's disease is a widespread, disabling, neurodegenerative disease induced by dopaminergic neuron loss and is linked to progressive motor impairment. Recently, genome‐editing technology like clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 has improved the translational gap in the treatments mediated through gene therapy. The advantages of the CRISPR system, such as, work in the living cells and tissues.

Background In vitro fertilization (IVF) with preimplantation genetic testing (PGT) has markedly improved clinical pregnancy outcomes for carriers of gene mutations or chromosomal structural rearrangements by the selection of embryos free of disease‐causing genes and chromosome abnormalities. However, for detecting whole or segmental chromosome aneuploidies, gene variants or balanced chromosome rearrangements in the same embryo require separate procedures, and none of the existing detection platforms is universal for all patients with different genetic disorders. Methods Here, we report a cost‐effective, family‐based haplotype phasing approach that can simultaneously evaluate multiple genetic variants, including monogenic disorders, aneuploidy, and balanced chromosome rearrangements in the same embryo with a single test. A total of 12 monogenic diseases carrier couples and either of them carried chromosomal rearrangements were enrolled simultaneously in this present study. Genome‐wide genotyping was performed with single‐nucleotide polymorphism (SNP)‐array, and aneuploidies were analyzed through SNP allele frequency and Log R ratio. Parental haplotypes were phased by an available genotype from a close relative, and the embryonic genome‐wide haplotypes were determined through family haplotype linkage analysis (FHLA). Disease‐causing genes and chromosomal rearrangements were detected by haplotypes located within the 2 Mb region covering the targeted genes or breakpoint regions. Results Twelve blastocysts were thawed, and then transferred into the uterus of female patients. Nine pregnancies had reached the second trimester and five healthy babies have been born. Fetus validation results, performed with the amniotic fluid or umbilical cord blood samples, were consistent with those at the blastocyst stage diagnosed by PGT. Conclusions We demonstrate that SNP‐based FHLA enables the accurate genetic detection of a wide spectrum of monogenic diseases and chromosome abnormalities in embryos, preventing the transfer of parental genetic abnormalities to the fetus. This method can be implemented as a universal platform for embryo testing in patients with different genetic disorders., 1. We report a cost‐effective, comprehensive, and universal platform for embryo testing in patients with different genetic disorders. 2. SNP‐based FHLA enables the accurate genetic detection for a wide spectrum of monogenic diseases and chromosome rearrangements in embryos. 3. This proposed strategy may markedly improve the precision of embryo testing and prevent the birth of affected fetuses.

Summary Photosynthesis is a key reaction that ultimately generates the carbohydrates needed to form woody tissues in trees. However, the genetic regulatory network of protein‐encoding genes (PEGs) and regulatory noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), underlying the photosynthetic pathway is unknown. Here, we integrated data from coexpression analysis, association studies (additive, dominance and epistasis), and expression quantitative trait nucleotide (eQTN) mapping to dissect the causal variants and genetic interaction network underlying photosynthesis in Populus. We initially used 30 PEGs, 6 miRNAs and 12 lncRNAs to construct a coexpression network based on the tissue‐specific gene expression profiles of 15 Populus samples. Then, we performed association studies using a natural population of 435 unrelated Populus tomentosa individuals, and identified 72 significant associations (P ≤ 0.001, q ≤ 0.05) with diverse additive and dominance patterns underlying photosynthesis‐related traits. Analysis of epistasis and eQTNs revealed that the complex genetic interactions in the coexpression network contribute to phenotypes at various levels. Finally, we demonstrated that heterologously expressing the most highly linked gene (PtoPsbX1) in this network significantly improved photosynthesis in Arabidopsis thaliana, pointing to the functional role of PtoPsbX1 in the photosynthetic pathway. This study provides an integrated strategy for dissecting a complex genetic interaction network, which should accelerate marker‐assisted breeding efforts to genetically improve woody plants.

OBJECTIVES Bipolar disorder (BD) is a neuropsychiatric disorder with a complex pattern of inheritance. Although many genetic studies have been conducted on BD, its genetic correlates remain uncertain. This study was aimed at identifying the genetic underpinnings of the disorder in an Indian family, which has been under comprehensive clinical evaluation and follow-up for over 12 years. METHODS We analysed a four-generation family with several of its members diagnosed for BD employing a combination of genetic linkage and exome analysis. RESULTS We obtained suggestive LOD score for a chromosome 1 and a chromosome 6 marker (D1S410; LOD = 3.01, Ө = 0; and D6S289; LOD = 1.58, Ө = 0). Manual haplotyping of the regions encompassing these two markers helped delimit a critical genomic interval of 32.44 Mb (D1S2700-D1S435; chromosome 1p31.1-13.2) and another of 10.34 Mb (D6S470-D6S422; chromosome 6p22.3-22.2). We examined the exomic sequences corresponding to these two intervals and found rare variants, NM_181712.4: c.2461G>T (p.Asp821Tyr) in KANK4 at 1p31.1-13.2; and NM_006366:c.-93G>A, in the 5' UTR of CAP2 at 6p22.3-22.2. CONCLUSIONS Our studysuggests involvement of KANK4 or CAP2 or both in BD in this family. Further analysis of these two genes in BD patients and functional evaluation of the allelic variants identified are suggested.

Chronic Intestinal Pseudo-Obstruction (CIPO) is a rare gastrointestinal disorder, which affects the smooth muscle contractions of the gastrointestinal tract. Dominant mutations in the smooth muscle actin gene, ACTG2, accounts for 44%-50% of CIPO patients. Other recessive or X-linked genes, including MYLK, LMOD1, RAD21, MYH11, MYL9, and FLNA were reported in single cases. In this study, we used Whole-Exome Sequencing (WES) to study 23 independent CIPO families including one extended family with 13 affected members. A dominantly inherited rare mutation, c.5819delC (p.Pro1940HisfsTer91), in the smooth muscle myosin gene, MYH11, was found in the extended family, shared by 7 affected family members but not by 3 unaffected family members with available DNA, suggesting a high probability of genetic linkage. Gene burden analysis indicates that additional genes, COL4A1, FBLN1 and HK2, may be associated with the disease. This study expanded our understanding of CIPO etiology and provided additional genetic evidence to physicians and genetic counselors for CIPO diagnosis.

Colorectal cancer (CRC), prostate cancer (PrC), and gastric cancer (GC) are common worldwide, and the incidence is to a certain extent dependent on genetics. We have recently shown that in families with more than one case of CRC, the risk of other malignancies is increased. We therefore suggested the presence of not yet described CRC syndromes. In this study, we have searched for genetic susceptibility loci for potential cancer syndromes involving CRC combined with PrC and/or GC. We have performed SNP (single‐nucleotide polymorphism)‐based linkage analyses in 45 families with CRC, PrC, and GC. In the regions with suggested linkage, we performed exome and association haplotype analyses. Five loci generated a high logarithm of odds (HLOD) score >2, suggestive of linkage, in chromosome bands 1q31‐32, 1q24‐25, 6q25‐26, 18p11‐q11, and Xp11. Exome analysis detected no potential pathogenic sequence variants. The haplotype association study showed that one of the top five haplotypes with the lowest P value in the chromosome band 6q25 interestingly was found in the family which contributed the most to the increased HLOD at that locus. This study supports a suggested hereditary cancer syndrome involving CRC and PrC and indicates a location at 6q25. The impact of this locus needs to be confirmed in additional studies.