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The article presents a study that analyzes the link between chromosome region 2p25 and type 1 diabetes (T1D). A 15-member family from Antioquia, Colombia and an independent sample diagnosed with T1D were analyzed. Radio immuno assay was applied to test anti-glutamic acid decarboxilase (GAD) antibodies in sera samples. The study concludes that genetic analysis of the subjects has indicated the presence of a T1D-related locus on 2p25 and thus associating 2p25 with T1D.

Genetic variants in the brain-derived neurotrophic factor (BDNF) gene, predominantly the functional Val66Met polymorphism, have been associated with risk of bipolar disorder and other psychiatric disorders. However, not all studies support these findings, and overall the evidence for the association of BDNF with disease risk is weak. As differences in population genetic structure between patient samples could cause discrepant or spurious association results, we investigated this possibility by carrying out population genetic analyses of the BDNF genomic region. Substantial variation was detected in BDNF coding region single-nucleotide polymorphism (SNP) allele and haplotype frequencies between 58 global populations, with the derived Met allele of Val66Met ranging in frequency from 0 to 72% across populations. FST analyses to assess diversity in the HapMap populations determined that the Val66Met FST value was at the 99.8th percentile among all SNPs in the genome. As the BDNF population genetic differences may be due to local selection, we performed the long-range haplotype test for selection using 68 SNPs spanning the BDNF genomic region in 12 European-derived pedigrees. Evidence for positive selection was found for a high-frequency Val-carrying haplotype, with a relative extended haplotype homozygosity value above the 99th percentile compared with HapMap data (P=4.6 × 10−4). In conclusion, we observed considerable BDNF allele and haplotype diversity among global populations and evidence for positive selection at the BDNF locus. These phenomena can have a profound impact on the detection of disease susceptibility genes and must be considered in gene association studies of BDNF. [ABSTRACT FROM AUTHOR]

Bipolar affective disorder is a heritable, relatively common, severe mood disorder with lifetime prevalence up to 4%. We report the results of a genome-wide linkage analysis conducted on a cohort of 35 Australian bipolar disorder families which identified evidence of significant linkage on chromosome 15q25-26 and suggestive evidence of linkage on chromosomes 4q, 6q and 13q. Subsequent fine-mapping of the chromosome 15q markers, using allele frequencies calculated from our cohort, gave significant results with a maximum two-point LOD score of 3.38 and multipoint LOD score of 4.58 for marker D15S130. Haplotype analysis based on pedigree-specific, identical-by-descent allele sharing, supported the location of a bipolar susceptibility gene within the Zmax−1 linkage confidence interval of 17 cM, or 6.2 Mb, between markers D15S979 and D15S816. Non-parametric and affecteds-only linkage analysis further verified the linkage signal in this region. A maximum NPL score of 3.38 (P=0.0008) obtained at 107.16 cM (near D15S130), and a maximum two-point LOD score of 2.97 obtained at marker D15S1004 (affecteds only), support the original genome-wide findings on chromosome 15q. These results are consistent with four independent positive linkage studies of mood and psychotic disorders, and raise the possibility that a common gene for susceptibility to bipolar disorder, and other psychiatric disorders may lie in this chromosome 15q25–26 region.Molecular Psychiatry (2009) 14, 492–500; doi:10.1038/sj.mp.4002146; published online 29 January 2008 [ABSTRACT FROM AUTHOR]

The DYX2 locus on chromosome 6p22.2 is the most replicated region of linkage to developmental dyslexia (DD). Two candidate genes within this region have recently been implicated in the disorder: KIAA0319 and DCDC2. Variants within DCDC2 have shown association with DD in a US and a German sample. However, when we genotyped these specific variants in two large, independent UK samples, we obtained only weak, inconsistent evidence for their involvement in DD. Having previously found evidence that variation in the KIAA0319 gene confers susceptibility to DD, we sought to refine this genetic association by genotyping 36 additional SNPs in the gene. Nine SNPs, predominantly clustered around the first exon, showed the most significant association with DD in one or both UK samples, including rs3212236 in the 5′ flanking region (P=0.00003) and rs761100 in intron 1 (P=0.0004). We have thus refined the region of association with developmental dyslexia to putative regulatory sequences around the first exon of the KIAA0319 gene, supporting the presence of functional mutations that could affect gene expression. Our data also suggests a possible interaction between KIAA0319 and DCDC2, which requires further testing.Molecular Psychiatry (2006) 11, 1085–1091. doi:10.1038/sj.mp.4001904; published online 10 October 2006 [ABSTRACT FROM AUTHOR]

Epidemiological twin studies demonstrate that autism spectrum disorders (ASDs) represent genetic disorders. Subsequent analyses indicate that the causes of ASDs include less common single-gene mutations and chromosomal abnormalities, as well as ASDs caused by multiple interacting genes of weak effect. Genome-wide linkage analysis has identified several susceptibility loci for the ASDs, and positional and functional candidate genes have been identified that appear to represent susceptibility genes for the ASDs. Analysis of additional larger samples and the use of genome-wide association and high-throughput variant detection will lead to the identification of further genes for ASDs. [ABSTRACT FROM AUTHOR]

The involvement of genetic factors in the etiology of autism has been clearly established. We undertook a genome-wide search for regions containing susceptibility genes for autism in 12 subjects with childhood autism and related pervasive developmental disorders (PDDs) and 44 controls from the relatively isolated population of the Faroe Islands. In total, 601 microsatellite markers distributed throughout the human genome with an average distance of 5.80 cM were genotyped, including 502 markers in the initial scan. The Faroese population structure and genetic relatedness of cases and controls were also evaluated. Based on a combined approach, including an assumption-free test as implemented in CLUMP, Fisher's exact test for specific alleles and haplotypes, and IBD0 probability calculations, we found association between autism and microsatellite markers in regions on 2q, 3p, 6q, 15q, 16p, and 18q. The most significant finding was on 3p25.3 (PT1=0.00003 and PT4=0.00007), which was also supported by other genetic studies. Furthermore, no evidence of population substructure was found, and a higher degree of relatedness among cases could not be detected, decreasing the risk of inflated P-values. Our data suggest that markers in these regions are in linkage disequilibrium with genes involved in the etiology of autism, and we hypothesize susceptibility genes for autism and related PDDs to be localized within these regions.Molecular Psychiatry (2006) 11, 37–46. doi:10.1038/sj.mp.4001754; published online 4 October 2005 [ABSTRACT FROM AUTHOR]

After the identification of the apolipoprotein E gene isoform (APOE-ε4) as a risk factor for late-onset Alzheimer’s disease (LOAD), the search for other polymorphisms associated with AD has been undertaken by many groups of investigators around the world. These studies have shown controversial results in many populations. More recently, a single nucleotide polymorphism in the promoter region of the brain-derived neurotrophin factor (BDNF) was found to be a risk factor for AD in two independent population studies. Here we report the analysis of this polymorphism in a group of 188 LOAD Brazilian patients compared to matched normal controls. A strong association between the APOE-ε4 polymorphism and LOAD was observed, but there was no significant association between this BNDF polymorphism and affected patients. The possibility that other polymorphisms or mutations in this gene play a role in the development of AD cannot be ruled out. However, the results of the present study suggest that in opposition to the two reported studies, this polymorphism does not seem to be implicated in LOAD Brazilian patients. It also shows the importance of replication studies in different populations, as susceptibility loci might differ in different ethnic groups; this will have important implications in future treatments with pharmacological agents. [ABSTRACT FROM AUTHOR]

Patients with schizophrenia (n=11) and bipolar affective disorder (n=17) from the relatively isolated population of the Faroe Islands were genotyped for 34 polymorphic markers on chromosome 4 in a search for allelic association and haplotype sharing among distantly related patients. When considering bipolar patients only, there was no clearcut support for any region on chromosome 4. The two-marker segment D4S394-D4S2983 at 4p16.1 was, however, supported by a P-value of 0.0162. For patients with schizophrenia, there was reasonable support for 4p16.1 as marker D4S2281 (P=0.0019), a two-marker segment (D4S2281-D4S1605, P=0.0009) and a three-marker segment (D4S2923-D4S2928-D4S1582, P-0.0005) appeared to be associated with schizophrenia, with some alleles/haplotypes occurring with different frequencies in patients compared to controls. When combining both psychiatric disorders, chromosome 4p16.1 received further support from five partially overlapping two- and three-marker segments (D4S394-D4S2983, P=0.0039; D4S2281-D4S1605, P=0.0027 and D4S394-D4S2983-D4S2923, P=0.006; D4S2923-D4S2928-D4S1582, P=0.00007; D4S1582-D4S1599-D4S2281, P=0.005). Increased haplotype sharing in patients with schizophrenia and in the combined data set was partly supported by Fisher's exact test and tests based on the genealogy. Our study yields support for a common risk gene for schizophrenia and bipolar affective disorder on the short arm of chromosome 4, as suggested by previous findings in the neighbouring Scottish population.Molecular Psychiatry (2004) 9, 93-98. doi:10.1038/sj.mp.4001393 [ABSTRACT FROM AUTHOR]