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Genomics in the Journals: 2013.06.20

NEW YORK (GenomeWeb News) – An albino Western lowland gorilla nicknamed Snowflake was likely the product of inbreeding between wild gorillas, according to a genome sequencing study in BMC Genomics.

The gorilla, born in the wilds of Equatorial Guinea, made his home at a zoo in Barcelona for nearly four decades. His white hair, pink skin, pale eyes, vision problems, sensitivity to light, and other features prompted a diagnosis of non-syndromic oculocutaneous albinism.

By sequencing Snowflake's genome to an average depth of nearly 19-fold and comparing it with the human reference genome, researchers traced the gorilla's albinism back to a single nucleotide change in a membrane transport-coding gene called SLC45A2. That swap alters the sequence of the resulting protein, they found, a transporter that is involved in oculocutaneous albinism type 4 in humans.

"We provided several lines of evidence … that this mutation in a transmembrane domain can modify the topology of the translated protein, therefore reinforcing its causative role in this rare case of albinism," the study's authors wrote.

"Moreover, long runs of homozygosity in this wild-born individual explain the emergence of this recessive trait through identity by descent," they added, "suggesting that inbreeding was an important factor towards the emergence of this phenotype."


In the Journal of Clinical Investigation, a University of Texas MD Anderson Cancer Center and Wellcome Trust Sanger Institute-led team reported on findings from an exome-sequencing study of a rare cancer called adenoid cystic carcinoma, which most often presents itself in salivary glands.

For their new analysis of ACC, researchers performed whole-exome sequencing on 23 primary ACC tumors and one ACC tumor that had metastasized to the lymph node. Compared to matched normal samples from the same cases, they found that tumors were particularly prone to mutations in chromatin-related genes. All told, they tracked down mutations affecting chromatin regulatory players in roughly half of cases tested.

The analysis unearthed recurrent translocation-related activation of the MYB gene, too — a glitch described in ACC tumors in the past. It also highlighted point mutations in new genes as well as genes previously implicated in cancer, including PIK3CA, NOTCH 1 and 2, and FGFR2.

Activating mutations in the latter gene may offer a possible target for treatment, study authors noted, since inhibitors of that receptor tyrosine kinase are already being tested for other conditions.


Members of the Cohorts for Heart and Aging Research in Genetic Epidemiology, or CHARGE, consortium used whole-genome sequencing to identify rare and common genetic variants contributing to high-density lipoprotein cholesterol levels in the blood — work that they described in Nature Genetics.

The researchers did low-coverage genome sequencing on 962 individuals enrolled in CHARGE studies. From the 25 million or so variants detected in these sequences, they determined that common variants likely have a more pronounced effect on the heritability of HDL-C levels than do rare variants.

In particular, the team estimated that almost 62 percent of heritability for this trait has its roots in common variants. In contrast, rare variants appear to explain around 8 percent of HDL-C level heritability.

Several variants with ties to HDL-C levels also turned up outside of known protein-coding sequencing, the study's authors noted, suggesting that at least some aspects of HDL-C levels are linked to specific regulatory sequences.

"Whole-genome sequencing analyses highlight the value of regulatory and non-protein-coding regions of the genome in addition to protein-coding regions," corresponding author Eric Boerwinkle, a researcher affiliated with the University of Texas Health Science Center at Houston and the Baylor College of Medicine, and his colleagues wrote.


An mBio study suggests that a subset of acute central nervous system infections found in individuals in Vietnam can be attributed to a previously undocumented virus from the Cyclovirus genus that is currently being called cyclovirus-Vietnam, or CyCV-VN.

Researchers from the UK, Vietnam, and the Netherlands first got wind of the virus when they used high-throughput sequencing — together with a virus identification method called amplified fragment length polymorphism — to test pooled cerebrospinal fluid samples from five Vietnamese patients with mysterious central nervous system infections.

After finding traces of the virus, investigators went on to sequence and assess CyCV-VN's full genome using cerebral spinal fluid samples from two of those patients, before looking at its prevalence in patients and other populations in Vietnam.

When the team tested samples from several hundred Vietnamese patients, for instance, it detected the new virus in around 4 percent of samples from those with known or suspected central nervous system infections. On the other hand, CyCV-VN sequences did not show up in samples from individuals who had neurological conditions stemming from non-infectious sources.

The virus turned up in fecal samples from apparently healthy children and agricultural animals too, the study's authors noted, pointing to possible food-related transmission of the virus from animal reservoirs. Nearly 60 percent of fecal samples from pigs and poultry contained viral sequences from CyCV-VN.


Genomics In The Journals is a weekly feature pointing readers to select, recently published articles involving genomics and related research.