Array-Based Comparative Genomic Hybridization (aCGH).

Copy number variations (CNVs) in the genomes have been suggested to play important roles in human evolution, genetic diversity, and disease susceptibility. A number of assays have been developed for the detection of CNVs, including fluorescent in situ hybridization (FISH), array-based comparative genomic hybridization (aCGH), PCR-based assays, and next-generation sequencing (NGS). In this chapter, we describe a microarray method that has been used for the detection of genome-wide CNVs, loss of heterozygosity (LOH), and uniparental disomy (UPD) associated with constitutional and neoplastic disorders. Methods Mol Biol. 2017;1541:167-179

Punctuated bursts in human male demography inferred from 1,244 worldwide Y-chromosome sequences

We report the sequences of 1,244 human Y chromosomes randomly ascertained from 26 worldwide populations by the 1000 Genomes Project. We discovered more than 65,000 variants, including single-nucleotide variants, multiple-nucleotide variants, insertions and deletions, short tandem repeats, and copy number variants. Of these, copy number variants contribute the greatest predicted functional impact. We constructed a calibrated phylogenetic tree on the basis of binary single-nucleotide variants and projected the more complex variants onto it, estimating the number of mutations for each class. Our phylogeny shows bursts of extreme expansion in male numbers that have occurred independently among each of the five continental superpopulations examined, at times of known migrations and technological innovations

Punctuated bursts in human male demography inferred from 1,244 worldwide Y-chromosome sequences

We report the sequences of 1,244 human Y chromosomes randomly ascertained from 26 worldwide populations by the 1000 Genomes Project. We discovered more than 65,000 variants, including single-nucleotide variants, multiple-nucleotide variants, insertions and deletions, short tandem repeats, and copy number variants. Of these, copy number variants contribute the greatest predicted functional impact. We constructed a calibrated phylogenetic tree on the basis of binary single-nucleotide variants and projected the more complex variants onto it, estimating the number of mutations for each class. Our phylogeny shows bursts of extreme expansion in male numbers that have occurred independently among each of the five continental superpopulations examined, at times of known migrations and technological innovations

An integrated map of structural variation in 2,504 human genomes

Summary Structural variants (SVs) are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight SV 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. Analyzing this set, we identify numerous gene-intersecting SVs exhibiting population stratification and describe naturally occurring homozygous gene knockouts suggesting the dispensability of a variety of human genes. We demonstrate that SVs are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of SV complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex SVs with multiple breakpoints likely formed through individual mutational events. Our catalog will enhance future studies into SV demography, functional impact and disease association