RESUMO
Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.
Assuntos
Variação Genética/genética , Genoma Humano/genética , Mapeamento Físico do Cromossomo , Sequência de Aminoácidos , Predisposição Genética para Doença , Genética Médica , Genética Populacional , Estudo de Associação Genômica Ampla , Genômica , Genótipo , Haplótipos/genética , Homozigoto , Humanos , Dados de Sequência Molecular , Taxa de Mutação , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Análise de Sequência de DNA , Deleção de Sequência/genéticaRESUMO
BACKGROUND: Turkey is a crossroads of major population movements throughout history and has been a hotspot of cultural interactions. Several studies have investigated the complex population history of Turkey through a limited set of genetic markers. However, to date, there have been no studies to assess the genetic variation at the whole genome level using whole genome sequencing. Here, we present whole genome sequences of 16 Turkish individuals resequenced at high coverage (32×-48×). RESULTS: We show that the genetic variation of the contemporary Turkish population clusters with South European populations, as expected, but also shows signatures of relatively recent contribution from ancestral East Asian populations. In addition, we document a significant enrichment of non-synonymous private alleles, consistent with recent observations in European populations. A number of variants associated with skin color and total cholesterol levels show frequency differentiation between the Turkish populations and European populations. Furthermore, we have analyzed the 17q21.31 inversion polymorphism region (MAPT locus) and found increased allele frequency of 31.25% for H1/H2 inversion polymorphism when compared to European populations that show about 25% of allele frequency. CONCLUSION: This study provides the first map of common genetic variation from 16 western Asian individuals and thus helps fill an important geographical gap in analyzing natural human variation and human migration. Our data will help develop population-specific experimental designs for studies investigating disease associations and demographic history in Turkey.
Assuntos
Alelos , Genética Populacional , Genoma Humano/genética , Análise de Sequência de DNA/métodos , África , Ásia , Europa (Continente) , Frequência do Gene , Estudo de Associação Genômica Ampla , Geografia , Humanos , Nucleotídeos/genética , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , TurquiaRESUMO
DNA sequencing technologies hold great promise in generating information that will guide scientists to understand how the genome effects human health and organismal evolution. The process of generating raw genome sequence data becomes cheaper and faster, but more error-prone. Assembly of such data into high-quality finished genome sequences remains challenging. Many genome assembly tools are available, but they differ in terms of their performance and their final output. More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. Here we evaluate the accuracies of several genome scaffolding algorithms using two different types of data generated from the genome of the same human individual: whole genome shotgun sequencing (WGS) and pooled clone sequencing (PCS). We observe that it is possible to obtain better assemblies if PCS data are used, compared to using only WGS data. However, the current scaffolding algorithms are developed only for WGS, and PCS-aware scaffolding algorithms remain an open problem.