Search

Next-generation sequencing (NGS) technologies have transformed medical genetics. However, short-read lengths pose a limitation on identification of structural variants, sequencing repetitive regions, phasing of distant nucleotide changes, and distinguishing highly homologous genomic regions. Long-read sequencing technologies may offer improvements in the characterization of genes that are currently difficult to assess. We used a combination of targeted DNA capture, long-read sequencing, and a customized bioinformatics pipeline to fully assemble the RH region, which harbors variation relevant to red cell donor-recipient mismatch, particularly among patients with sickle cell disease. RHD and RHCE are a pair of duplicated genes located within an ∼175 kb region on human chromosome 1 that have high sequence similarity and frequent structural variations. To achieve the assembly, we utilized palindrome repeats in PacBio SMRT reads to obtain consensus sequences of 2.1 to 2.9 kb average length with over 99% accuracy. We used these long consensus sequences to identify 771 assembly markers and to phase the RHD-RHCE region with high confidence. The dataset enabled direct linkage between coding and intronic variants, phasing of distant SNPs to determine RHD-RHCE haplotypes, and identification of known and novel structural variations along with the breakpoints. A limiting factor in phasing is the frequency of heterozygous assembly markers and therefore was most successful in samples from African Black individuals with increased heterogeneity at the RH locus. Overall, this approach allows RH genotyping and de novo assembly in an unbiased and comprehensive manner that is necessary to expand application of NGS technology to high-resolution RH typing., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

The domestic dog, as a highly successful domestication model, is well known as a favored human companion. Exploring its domestication history should provide great insight into our understanding of the prehistoric development of human culture and productivity. Furthermore, investigation on the mechanisms underpinning the morphological and behavioral traits associated with canid domestication syndrome is of significance not only for scientific study but also for human medical research. Current development of a multidisciplinary canine genome database, which includes enormous omics data, has substantially improved our understanding of the genetic makeup of dogs. Here, we reviewed recent advances associated with the original history and genetic basis underlying environmental adaptations and phenotypic diversities in domestic dogs, which should provide perspectives on improving the communicative relationship between dogs and humans.

Background: Gene flow in plants via pollen and seeds is asymmetrical at different geographic scales. Orchid seeds are adapted to long-distance wind dispersal but pollinium transfer is often influenced by pollinator behavior. We combined field studies with an analysis of genetic diversity among 155 physically mapped adults and 1105 F1 seedlings to evaluate the relative contribution of pollen and seed dispersal to overall gene flow among three sub-populations of the food-deceptive orchid Phalaenopsis pulcherrima on Hainan Island, China., Results: Phalaenopsis pulcherrima is self-sterile and predominantly outcrossing, resulting in high population-level genetic diversity, but plants are clumped and exhibit fine-scale genetic structuring. Even so, we detected low differentiation among sub-populations, with polynomial regression analysis suggesting gene flow via seed to be more restricted than that via pollen. Paternity analysis confirmed capsules of P. pulcherrima to each be sired by a single pollen donor, probably in part facilitated by post-pollination stigma obfuscation, with a mean pollen flow distance of 272.7 m. Despite limited sampling, we detected no loss of genetic diversity from one generation to the next., Conclusions: Outcrossing mediated by deceptive pollination and self-sterility promote high genetic diversity in P. pulcherrima. Long-range pollinia transfer ensures connectivity among sub-populations, offsetting the risk of genetic erosion at local scales.

The correlation of genetic alterations with response to neoadjuvant chemotherapy (NAC) has not been fully revealed. In this study, we enrolled 247 breast cancer patients receiving anthracycline-taxane-based NAC treatment. A next generation sequencing (NGS) panel containing 36 hotspot breast cancer-related genes was used in this study. Two different standards for the extent of pathologic complete response (pCR), ypT0/isypN0 and ypT0/is, were used as indicators for NAC treatment. TP53 mutation (n = 149, 60.3%), PIK3CA mutation (n = 109, 44.1%) and MYC amplification (n = 95, 38.5%) were frequently detected in enrolled cases. TP53 mutation (P = 0.019 for ypT0/isypN0 and P = 0.003 for ypT0/is) and ERBB2 amplification (P < 0.001 for both ypT0/isypN0 and ypT0/is) were related to higher pCR rates. PIK3CA mutation (P = 0.040 for ypT0/isypN0) and CCND2 amplification (P = 0.042 for ypT0/is) showed reduced sensitivity to NAC. Patients with MAPK pathway alteration had low pCR rates (P = 0.043 for ypT0/is). Patients with TP53 mutation (-) PIK3CA mutation (-) ERBB2 amplification (+) CCND1 amplification (-), TP53 mutation (+) PIK3CA mutation (-) ERBB2 amplification (+) CCND1 amplification (-) or TP53 mutation (+) PIK3CA mutation (+) ERBB2 amplification (+) CCND1 amplification (-)had significantly higher pCR rates (P < 0.05 for ypT0/isypN0 and ypT0/is) than wild type genotype tumors. Some cancer genetic alterations as well as pathway alterations were associated with chemosensitivity to NAC treatment. Our study may shed light on the molecular characteristics of breast cancer for prediction of NAC expectations when breast cancer is first diagnosed by biopsy., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

There are several indigenous ethnic populations along the silk road in the Northwest of China that display clear differences in culture and social customs, perhaps as a result of geographic isolation and different linguistic traditions. However, extensive trade and other interactions probably facilitated the admixture of different gene pools between these populations over the last two millennia. To further explore the evolutionary relationships of the 13 ethnic populations residing in Northwest China and to reveal the features of population admixture, the 9 most-commonly employed CODIS loci (D3S1358, TH01, D5S818, D13S317, D7S820, CSF1PO, vWA, TPOX, FGA) were selected for genotyping and further analysis. Phylogenetic tree and principal component analysis revealed clear pattern of population differentiation between 4 populations living in Sinkiang Uighur Autonomous Region and other 9 populations dwelled in the upper regions of Silk Road. R matrix regression showed high-level gene flow and population admixture dose exist among these ethic populations in the Northwest region of China. Furthermore, the Mantel test suggests that larger percent of genetic variance (21.58% versus 2.3%) can be explained by geographic isolation than linguistic barriers, which matched with the contribution of geographic factors to other world populations.

Background: The reliance on a solitary linear reference genome has imposed a significant constraint on our comprehensive understanding of genetic variation in animals. This constraint is particularly pronounced for non-reference sequences (NRSs), which have not been extensively studied. Results: In this study, we constructed a pig pangenome graph using 21 pig assemblies and identified 23,831 NRSs with a total length of 105 Mb. Our findings revealed that NRSs were more prevalent in breeds exhibiting greater genetic divergence from the reference genome. Furthermore, we observed that NRSs were rarely found within coding sequences, while NRS insertions were enriched in immune-related Gene Ontology terms. Notably, our investigation also unveiled a close association between novel genes and the immune capacity of pigs. We observed substantial differences in terms of frequencies of NRSs between Eastern and Western pigs, and the heat-resistant pigs exhibited a substantial number of NRS insertions in an 11.6 Mb interval on chromosome X. Additionally, we discovered a 665 bp insertion in the fourth intron of the TNFRSF19 gene that may be associated with the ability of heat tolerance in Southern Chinese pigs. Conclusions: Our findings demonstrate the potential of a graph genome approach to reveal important functional features of NRSs in pig populations. [ABSTRACT FROM AUTHOR]

The whiteleg shrimp (Litopenaeus vannamei) is one of the most economically important aquaculture species in China. Genetic diversity is crucial for maintaining the gene pool of farmed shrimp. In this study, the effects of artificial selection on the genetic structure of four whiteleg shrimp strains were evaluated using microsatellite sequences. The results showed that the observed heterozygosity (Ho), expected heterozygosity (He), and the polymorphism information content (PIC) of the four selected strains ranged from 0.446 to 0.574, 0.450 to 0.566, and 0.435 to 0.509, respectively. All the selected strains maintained a moderate level of genetic diversity. Most inbreeding coefficients (Fis) in the four strains were positive but not significantly different from zero, indicating a relatively low degree of inbreeding within each strain. However, He and PIC in line 5 showed a decreasing trend from the 2017 to the 2019 generations, and Fis in line 10 showed a significant increasing trend across generations, indicating that measures must be taken to maintain the level of genetic diversity for lines 5 and 10. UPGMA cluster trees showed that the four breeding lines had apparent genetic differences, which could provide a genetic basis for studying crossbreeding between selective lines and the utilization of heterosis. This study will be useful for population genetic research and the breeding strategies of whiteleg shrimp. [ABSTRACT FROM AUTHOR]

Background: Domestication from wild rice species to cultivated rice is a key milestone, which involved changes of many specific traits and the variations of the genetic systems. Among the AA-genome wild rice species, O. rufipogon and O. nivara, have many favorable genes and thought to be progenitors of O. sativa. Results: In the present study, by using O. rufipogon and O. nivara as donors, the single segment substitution lines (SSSLs) have been developed in the background of the elite indica cultivar, HJX74. In the SSSLs population, 11 genes for 5 domestication traits, including tiller angle, spreading panicle, awn, seed shattering, and red pericarp, were identified and mapped on 5 chromosomes through substitution mapping. Herein, allelic variations of 7 genes were found through sequence alignment with the known genes, that is, TA7-RUF was allelic to PROG1, TA8-RUF was allelic to TIG1, SPR4-NIV was allelic to OsLG1, AN4-RUF was allelic to An-1, SH4-NIV was allelic to SH4, and both RC7-RUF and RC7-NIV were allelic to Rc. Meanwhile, 4 genes, TA11-NIV, SPR3-NIV, AN3-NIV, and AN4-NIV, were considered as the novel genes identified in these SSSLs, because of none known genes for the related domestication traits found in the chromosomal locations of them. Conclusion: The results indicated that the SSSLs would be precious germplasm resources for gene mining and utilization from wild rice species, and it laid the foundation for further analyses of the novel domestication genes to better understand the genetic basis in regulating the traits variation during domestication. [ABSTRACT FROM AUTHOR]

Chinese indigenous pig breeds have been undergoing selection for thousands of years, and have become invaluable genetic sources over the world. To investigate the population structure and genetic diversity of Jinhua (JH), Longyou Black (LYW), Shengxian Spotted (SXH), and Lanxi Spotted (LXH) breeds, a total of 200 pigs belonging to 10 diverse population were genotyped using SNP chips. The results showed that LYW pigs exhibited higher level of heterozygosity than the other indigenous pigs. In addition, gene introgression from intensively reared commercial pig breeds to LYW pigs was detected. Moreover, selection signature analysis revealed the possibility of differences between Chinese indigenous and intensively reared commercial pig breeds were mainly present for meat and carcass traits. Furthermore, we found that ANXA13, DISP1, and SRSF6 were the nearest genes located around the common selection signatures detected between each indigenous pig breed and Chinese wild boars. Our findings provide new insights into the selection signatures of Chinese indigenous pigs, and may contribute to future pig breeding. [ABSTRACT FROM AUTHOR]

Background: Compared to medium-density single nucleotide polymorphism (SNP) data, high-density SNP data contain abundant genetic variants and provide more information for the genetic evaluation of livestock, but it has been shown that they do not confer any advantage for genomic prediction and heritability estimation. One possible reason is the uneven distribution of the linkage disequilibrium (LD) along the genome, i.e., LD heterogeneity among regions. The aim of this study was to effectively use genome-wide SNP data for genomic prediction and heritability estimation by using models that control LD heterogeneity among regions. Methods: The LD-adjusted kinship (LDAK) and LD-stratified multicomponent (LDS) models were used to control LD heterogeneity among regions and were compared with the classical model that has no such control. Simulated and real traits of 2000 dairy cattle individuals with imputed high-density (770K) SNP data were used. Five types of phenotypes were simulated, which were controlled by very strongly, strongly, moderately, weakly and very weakly tagged causal variants, respectively. The performances of the models with high- and medium-density (50K) panels were compared to verify that the models that controlled LD heterogeneity among regions were more effective with high-density data. Results: Compared to the medium-density panel, the use of the high-density panel did not improve and even decreased prediction accuracies and heritability estimates from the classical model for both simulated and real traits. Compared to the classical model, LDS effectively improved the accuracy of genomic predictions and unbiasedness of heritability estimates, regardless of the genetic architecture of the trait. LDAK applies only to traits that are mainly controlled by weakly tagged causal variants, but is still less effective than LDS for this type of trait. Compared with the classical model, LDS improved prediction accuracy by about 13% for simulated phenotypes and by 0.3 to ~ 10.7% for real traits with the high-density panel, and by ~ 1% for simulated phenotypes and by − 0.1 to ~ 6.9% for real traits with the medium-density panel. Conclusions: Grouping SNPs based on regional LD to construct the LD-stratified multicomponent model can effectively eliminate the adverse effects of LD heterogeneity among regions, and greatly improve the efficiency of high-density SNP data for genomic prediction and heritability estimation. [ABSTRACT FROM AUTHOR]

Chinese indigenous pigs in the Taihu Lake region are well known for their high fecundity and other excellent characteristics. To better understand the characteristics of these breeds in this area as well as to provide the government and breeders the molecular basis for formulating a reasonable conservation policy, we explored the structure of haplotype blocks and genetic diversity of the 7 populations which is relevant for the management and conservation of these important genetic resources using next-generation sequencing data. In this study, a total of 131 300 single-nucleotide polymorphisms with minor allele frequencies ⩾0.05 were obtained for further analysis. In general, there are similar within-breed genetic diversities (He, Ho, Pn, Ar) among these 7 pig populations in the Taihu Lake region. Average values for the inbreeding coefficients estimates in the 7 populations are 0.110 (F1), 0.056 (F2), and 0.078 (F3). All the breeds have seen a continuous decline in Ne estimates over time with FJ and SW populations having a very similar curve. Moreover, the Ne of SMS pig breeds were smaller than other Chinese pig breeds, indicating that SMS pig breeds underwent stronger selection pressure than other Chinese pig breeds. The average genetic distances among the 7 populations in the Taihu Lake region were 0.235 (MMS), 0.240 (SMS), 0.269 (EH), 0.248 (MI), 0.221 (FJ), 0.254 (JX), and 0.212 (SW). A summary of the number of haplotype blocks and haplotype diversity was also presented. This study provide a deep understanding of the current situation of conservation in this region, thereby uncovering the pertinent insight to better formulate more reasonable preservation policies for the government departments and breeding planners to follow-up. [ABSTRACT FROM AUTHOR]

Ecotypes are the result of ecological differentiation at the early stages of speciation. Adaptation to soil conditions offers arguably the best examples of local adaptation in plants. Two sympatric ecotypes, with either a red or green abaxial leaf surface, were found without clear geographical isolation in Phalaenopsis pulcherrima, a Southeast Asia endemic and endangered orchid. The soil of the red leaf ecotype has a higher water content and nutrient content than the green ecotype. What is the genetic structure of the two ecotypes? Is there complete or partial reproductive isolation between the two ecotypes? In this work, leaf reflection of the two ecotypes in P. pulcherrima were compared, to illustrate their difference in leaf color. The genetic differentiation between two ecotypes was examined, using ISSR and SRAP markers to determine the genetic structure of the populations. Our results showed that the green ecotype had reflectance spectrum peaks at 530 nm and 620 nm, while in the red ecotype, the peak at 530 nm was absent. A total of 165 ISSR and SRAP loci showed a high level of genetic diversity within the green ecotype, and analyses of the population structure revealed two genetic clusters that corresponded to the red and green ecotypes. The percentage of variation between the two ecotypes (24.55%) was greater than the percentage of variation among the populations (16.54%)—indicating partial reproductive isolation, high genetic differentiation, and that ecological differentiation has been more important than geographical barriers among populations within ecotypes. Most pairwise FST values between the populations within either ecotype on Hainan Island were less than 0.15; however, the FST between both the Thai and Malaysian populations and the Hainan Island population was greater than 0.25, due to South China sea isolation. Ecotypic differentiation is an important part of speciation; therefore, we must take into account the axes along which lineages sort, when formulating protection strategies. [ABSTRACT FROM AUTHOR]