The Ser19Stop single nucleotide polymorphism (SNP) of human PHYHIPL affects the cerebellum in mice

The HapMap Project is a major international research effort to construct a resource to facilitate the discovery of relationships between human genetic variations and health and disease. The Ser19Stop single nucleotide polymorphism (SNP) of human phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL) gene was detected in HapMap project and registered in the dbSNP. PHYHIPL gene expression is altered in global ischemia and glioblastoma multiforme. However, the function of PHYHIPL is unknown. We generated PHYHIPL Ser19Stop knock-in mice and found that PHYHIPL impacts the morphology of cerebellar Purkinje cells (PCs), the innervation of climbing fibers to PCs, the inhibitory inputs to PCs from molecular layer interneurons, and motor learning ability. Thus, the Ser19Stop SNP of the PHYHIPL gene may be associated with cerebellum-related diseases.

The great tit HapMap project: a continental-scale analysis of genomic variation in a songbird

A major aim of evolutionary biology is to understand why patterns of genomic diversity vary among populations and species. Large-scale genomic studies of widespread species are useful for studying how the environment and demographic history shape patterns of genomic divergence, and with the continually decreasing cost of sequencing and genotyping, such studies are now becoming feasible. Here, we carry out one of the most geographically comprehensive surveys of genomic variation in a wild vertebrate to date; the great tit (Parus major) HapMap project. We screened ca 500,000 SNP markers across 647 individuals from 29 populations, spanning almost the entire geographic range of the European great tit subspecies. We found that genome-wide variation was consistent with a recent colonisation across Europe from a single refugium in South-East Europe, with bottlenecks and reduced genetic diversity in island populations. Differentiation across the genome was highly heterogeneous, with clear “islands of differentiation” even among populations with very low levels of genome-wide differentiation. Low local recombination rate in the genome was a strong predictor of high local genomic differentiation (FST), especially in island and peripheral mainland populations, suggesting that the interplay between genetic drift and recombination is a key driver of highly heterogeneous differentiation landscapes. We also detected genomic outlier regions that were confined to one or more peripheral great tit populations, most likely as a result of recent directional selection at the range edges of this species. Haplotype-based measures of selection were also related to recombination rate, albeit less strongly, and highlighted population-specific sweeps that likely resulted from positive selection. These regions under positive selection contained candidate genes associated with morphology, thermal adaptation and colouration, providing promising avenues for future investigation. Our study highlights how comprehensive screens of genomic variation in wild organisms can provide unique insights into evolution.

Length Distribution of Ancestral Tracks under a General Admixture Model and Its Applications in Population History Inference

The length of ancestral tracks decays with the passing of generations which can be used to infer population admixture histories. Previous studies have shown the power in recovering the histories of admixed populations via the length distributions of ancestral tracks even under simple models. We believe that the deduction of length distributions under a general model will greatly elevate the power. Here we first deduced the length distributions under a general model and proposed general principles in parameter estimation and model selection with the deduced length distributions. Next, we focused on studying the length distributions and its applications under three typical special cases. Extensive simulations showed that the length distributions of ancestral tracks were well predicted by our theoretical framework. We further developed a new method, AdmixInfer, based on the length distributions and good performance was observed when it was applied to infer population histories under the three typical models. Notably, our method was insensitive to demographic history, sample size and threshold to discard short tracks. Finally, good performance was also observed when applied to some real datasets of African Americans, Mexicans and South Asian populations from the HapMap project and the Human Genome Diversity Project.

The Associations of Novel Vitamin D3Metabolic GeneCYP27A1Polymorphism, Adiponectin/Leptin Ratio, and Metabolic Syndrome in Middle-Aged Taiwanese Males

Metabolic syndrome (MetS) confers increased risks of cardiovascular disease (CVD). Both vitamin D3and adipocytokines (especially adiponectin and leptin) have a great impact on CVD and MetS. In vitamin D3metabolism, the vitamin D325-hydroxylase (CYP27A1) and 25-hydroxyvitamin D31-alpha-hydroxylase (CYP27B1) are two key enzymes. This study aimed to examine the influence of vitamin D3CYP27 single nucleotide polymorphisms (SNPs) on adipocytokines and MetS. Cross-sectional data and DNA samples were collected from male volunteers (n=649, age: 55.7 ± 4.7 years). Two tagging SNPs,CYP27A1 rs4674344andCYP27B1 rs10877012, were selected from the HapMap project. MetS was significantly associated with theCYP27A1 rs4674344SNP(P=0.04)and the ratio of adiponectin/leptin (A/L ratio) was most correlated to theCYP27A1 rs4674344SNP, appearing to be significantly lower in T-carriers than in AA subjects (3.7 ± 4.0 versus 5.1 ± 6.0,P=0.001) and significantly negatively associated after adjustment. For each MetS component associated with theCYP27A1 rs4674344SNP, the A/L ratios were significantly negative in preclinical stage (condition not meeting the individual criteria), except the blood pressure. In conclusion,CYP27A1 rs4674344SNP, A/L ratio, and MetS are significantly associated and T-carriers might have a higher risk of developing MetS due to low A/L ratios in the preclinical stage.

Analysis of a Larger SNP Dataset from the HapMap Project Confirmed That the Modern Human A Allele of the ABO Blood Group Genes Is a Descendant of a Recombinant between B and O Alleles

The human ABO blood group gene consists of three main alleles (A, B, and O) that encode a glycosyltransferase. The A and B alleles differ by two critical amino acids in exon 7, and the major O allele has a single nucleotide deletion (Δ261) in exon 6. Previous evolutionary studies have revealed that the A allele is the most ancient, B allele diverged from the A allele with two critical amino acid substitutions in exon 7, and the major O allele diverged from the A allele with Δ261 in exon 6. However, a recent phylogenetic network analysis study showed that the A allele of humans emerged through a recombination between the B and O alleles. In the previous study, a restricted dataset from only two populations was used. In this study, therefore, we used a large single nucleotide polymorphism (SNP) dataset from the HapMap Project. The results indicated that the A101-A201-O09 haplogroup was a recombinant lineage between the B and O haplotypes, containing the intact exon 6 from the B allele and the two critical A type sites in exon 7 from the major O allele. Its recombination point was assumed to be located just behind Δ261 in exon 6.