Genetically influenced tobacco and alcohol use behaviors impact erythroid trait variation.

Genome wide association studies (GWAS) have associated thousands of loci with quantitative human blood trait variation. Loci and related genes that impact blood trait variation may regulate blood cell-intrinsic biological processes, or alternatively impact blood cell development and function via systemic factors. Clinical observations have linked tobacco or alcohol use with altered blood traits, but these trait relationships have not been systematically explored at the genetic level.

Assessing the Risk Stratification of Breast Cancer Polygenic Risk Scores in a Brazilian Cohort.

Polygenic risk scores (PRSs) for breast cancer have a clear clinical utility in risk prediction. PRS transferability across populations and ancestry groups is hampered by population-specific factors, ultimately leading to differences in variant effects, such as linkage disequilibrium and differences in variant frequency (allele frequency differences). Thus, locally sourced population-based phenotypic and genomic data sets are essential to assess the validity of PRSs derived from signals detected across populations.

Genetically influenced tobacco and alcohol use behaviors impact erythroid trait variation.

Genome wide association studies (GWAS) have associated thousands of loci with quantitative human blood trait variation. Blood trait associated loci and related genes may regulate blood cell-intrinsic biological processes, or alternatively impact blood cell development and function via systemic factors and disease processes. Clinical observations linking behaviors like tobacco or alcohol use with altered blood traits can be subject to bias, and these trait relationships have not been systematically explored at the genetic level.

Inferring Balancing Selection From Genome-Scale Data.

The identification of genomic regions and genes that have evolved under natural selection is a fundamental objective in the field of evolutionary genetics. While various approaches have been established for the detection of targets of positive selection, methods for identifying targets of balancing selection, a form of natural selection that preserves genetic and phenotypic diversity within populations, have yet to be fully developed. Despite this, balancing selection is increasingly acknowledged as a significant driver of diversity within populations, and the identification of its signatures in genomes is essential for understanding its role in evolution.

Polygenic Scores for Height in Admixed Populations.

Polygenic risk scores (PRS) use the results of genome-wide association studies (GWAS) to predict quantitative phenotypes or disease risk at an individual level, and provide a potential route to the use of genetic data in personalized medical care. However, a major barrier to the use of PRS is that the majority of GWAS come from cohorts of European ancestry. The predictive power of PRS constructed from these studies is substantially lower in non-European ancestry cohorts, although the reasons for this are unclear.

Evolutionary and functional impact of common polymorphic inversions in the human genome.

Inversions are one type of structural variants linked to phenotypic differences and adaptation in multiple organisms. However, there is still very little information about polymorphic inversions in the human genome due to the difficulty of their detection. Here, we develop a new high-throughput genotyping method based on probe hybridization and amplification, and we perform a complete study of 45 common human inversions of 0.

Signatures of Long-Term Balancing Selection in Human Genomes.

Balancing selection maintains advantageous diversity in populations through various mechanisms. Although extensively explored from a theoretical perspective, an empirical understanding of its prevalence and targets lags behind our knowledge of positive selection. Here, we describe the Non-central Deviation (NCD), a simple yet powerful statistic to detect long-term balancing selection (LTBS) that quantifies how close frequencies are to expectations under LTBS, and provides the basis for a neutrality test.

A genomic perspective on HLA evolution.

Several decades of research have convincingly shown that classical human leukocyte antigen (HLA) loci bear signatures of natural selection. Despite this conclusion, many questions remain regarding the type of selective regime acting on these loci, the time frame at which selection acts, and the functional connections between genetic variability and natural selection. In this review, we argue that genomic datasets, in particular those generated by next-generation sequencing (NGS) at the population scale, are transforming our understanding of HLA evolution.

Heterogeneity of dN/dS Ratios at the Classical HLA Class I Genes over Divergence Time and Across the Allelic Phylogeny.

The classical class I HLA loci of humans show an excess of nonsynonymous with respect to synonymous substitutions at codons of the antigen recognition site (ARS), a hallmark of adaptive evolution. Additionally, high polymporphism, linkage disequilibrium, and disease associations suggest that one or more balancing selection regimes have acted upon these genes. However, several questions about these selective regimes remain open.

HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms.

Supertypes are groups of human leukocyte antigen (HLA) alleles which bind overlapping sets of peptides due to sharing specific residues at the anchor positions-the B and F pockets-of the peptide-binding region (PBR). HLA alleles within the same supertype are expected to be functionally similar, while those from different supertypes are expected to be functionally distinct, presenting different sets of peptides. In this study, we applied the supertype classification to the HLA-A and HLA-B data of 55 worldwide populations in order to investigate the effect of natural selection on supertype rather than allelic variation at these loci.

Kiwi genome provides insights into evolution of a nocturnal lifestyle.

Background: Kiwi, comprising five species from the genus Apteryx, are endangered, ground-dwelling bird species endemic to New Zealand. They are the smallest and only nocturnal representatives of the ratites. The timing of kiwi adaptation to a nocturnal niche and the genomic innovations, which shaped sensory systems and morphology to allow this adaptation, are not yet fully understood.

Mapping Bias Overestimates Reference Allele Frequencies at the HLA Genes in the 1000 Genomes Project Phase I Data.

Next-generation sequencing (NGS) technologies have become the standard for data generation in studies of population genomics, as the 1000 Genomes Project (1000G). However, these techniques are known to be problematic when applied to highly polymorphic genomic regions, such as the human leukocyte antigen (HLA) genes. Because accurate genotype calls and allele frequency estimations are crucial to population genomics analyses, it is important to assess the reliability of NGS data.

Development of polymorphic microsatellite markers for the human botfly, Dermatobia hominis (Diptera: Oestridae).

In this report, we describe the development of 17 polymorphic microsatellite markers for the human botfly, Dermatobia hominis, an obligatory parasite of mammals of great veterinary importance in Latin America. The number of alleles ranged from 5 to 21 per locus, with a mean of 12.2 alleles per locus.