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Genomics in the Journals: Oct 23, 2014

NEW YORK (GenomeWeb) – In Nature Genetics, the University of Washington's Evan Eichler and colleagues from the US and Italy explored molecular mechanisms that can cause the genetic instability behind a notorious chromosome 15 region implicated in conditions that range from idiopathic generalized epilepsy to intellectual disability, schizophrenia, and autism spectrum disorder.

The team used read depth data from thousands of human, ape, and archaic hominin genomes to perform a copy number polymorphism profiling analysis. It also conducted detailed genomic analyses on 80 individuals with rare or common microdeletions in the region of interest, known as 15q13.3.

During their search for copy number polymorphic parts of the genome, the investigators found chromosome 15 sites neighboring a gene called GOLGA8 that were prone to human-specific segmental duplication expansions and inversions — copy number variations that seem to have been introduced relatively recently in the human lineage, leading to varied structural configurations at 15q13.3.

"We propose that the GOLGA core duplicons are preferential sites of genomic instability that have driven both disease and the evolutionary instability of chromosome 15," the study's authors wrote, noting that "[o]ur evolutionary reconstruction suggests that the GOLGA8 core duplicon in particular has promoted both inversions and the formation of large palindromic segmental duplication structures."

A Nature Communications study by researchers at Washington University and other centers in the US, UK, and France offered insights into the types of genes involved in the evolution of traits such as eyeless-ness, pigment loss, body size boosts, and behavioral shifts in the cavefish, Astyanax mexicanus.

The team used DNA from a fish born to two wild-caught parents from Pachón cave in Mexico to put together a 964-million-base de novo draft genome assembly for the blind cave fish, commonly called the Mexican tetra.

Using the genome sequence, along with RNA sequence data generated for several cavefish tissues, the group annotated an estimated 23,042 protein-coding genes and identified transposable element sequences that made up roughly one-third of the genome.

The study's authors also used the cave fish variant and gene expression data to narrow in on candidate genes that correspond to quantitative trait loci that have been linked to traits such as vibration attraction, muted coloring, and eye degeneration— information they hope will prove useful in understanding the human eye and degenerative conditions that can affect it.

"Many of [the characteristic cavefish] traits are really important for human health, such as the fishes' eye loss, which could be analogous to human diseases such as retinal degeneration," corresponding author Suzanne McGaugh said in a statement. McGaugh was affiliated with the Genome Institute at Washington University when the study was done. She is now doing ecology, evolution, and behavior research at the University of Minnesota.

A meta-analysis appearing in JAMA Pediatrics considered potential ties between genetic risk scores related to adult obesity and body size and/or composition at birth through five years of age.

Using data for more than 3,000 children enrolled through birth cohorts in England, France, and Spain, researchers from the University of Cambridge and elsewhere assessed genetic obesity risk based on information at 16 SNPs linked to adult body mass index patterns through past genome-wide association studies. They also considered body mass and composition features such as weight, BMI, lean mass, fat mass, height, and body fat at birth for these participants.

Results from the analysis suggest that associations between genetic obesity risk score and features such as weight, fat mass, and BMI tends to increase as children become older, though it did not appear to provide predictive information about an infant's birth size.

"Genetic obesity susceptibility appears to promote a normally partitioned increase in early postnatal, but not prenatal, growth," corresponding author Ken Ong, an epidemiology researcher with University of Cambridge, Addenbrooke's Hospital, and his colleagues wrote. "These findings suggest that symmetrical rapid growth may identify infants with high lifelong susceptibility for obesity."

An international team led by investigators in Ireland did genome sequencing on more than a dozen ancient human samples from Neolithic Age, Copper Age, Bronze Age, and Iron Age burial sites in Hungary to retrace population transitions on the Great Hungarian Plain over some 5,000 years.

As they reported in Nature Communications, the researchers sequenced DNA from dense, petrous inner ear bone samples from 13 Hungarian individuals, representing various stages of transition from a hunter-gatherer to agricultural lifestyle in the Great Hungarian Plain area, a well-traversed and archeologically rich region in southern and eastern Hungary.

With these samples, the team generated genome sequences that ranged in depth from 0.1-fold to more than 22-fold average coverage apiece, comparing these sequences to one another and to hundreds of other sequences or variant sets for ancient individuals from Europe, the Near East, and the Caucasus.

From the variants detected in the ancient Hungarian samples, authors of the study outlined genomic changes and apparent population patterns that marked each cultural transition.

For example, their findings suggest that variants associated with lighter skin pigmentation became more predominant as hunter-gatherer populations mixed with incoming agricultural individuals, though even the most recent samples did not carry known variants associated with the ability to digest the milk sugar lactose.

"[O]ur results … imply that the great changes in prehistoric technology, including the adoption of farming, followed by the first use of the hard metals, bronze and then iron, were each associated with the substantial influx of new people," co-corresponding author Dan Bradley, with the Trinity College Dublin Smurfit Institute of Genetics, said in a statement.

"We can no longer believe these fundamental innovations were simply absorbed by existing populations in a sort of cultural osmosis," Bradley added.