NEW YORK (GenomeWeb News) – In Nature Genetics, an international group led by investigators at the University of California at Los Angeles describes the targeted sequencing tactics it used to find mutations behind IMAGe syndrome, a developmental condition marked by diminutive size, underdeveloped organs, and abnormal adrenal gland function.
Using custom arrays, the team targeted coding sequences from a 22.6 million base stretch of chromosome 11 implicated through an identity-by-descent analysis on an affected Argentinean family. By sequencing the exons and splice sites in this chromosome 11 region in two family members with IMAGe syndrome and in unrelated individuals with the condition, researchers tracked down IMAGe-related mutations in CDKN1C, a gene previously linked to the excessive growth condition Beckwith-Wiedemann syndrome. Follow-up experiments confirmed the gene's role in IMAGe, indicating that the condition stems from alterations in a specific domain of the maternally inherited version of CDKN1C.
In the early, online edition of the American Journal of Psychiatry, American researchers explore the influence that variants in a cluster of chromosome 15 nicotine receptor genes have on individuals' success when trying to quit smoking.
By bringing data from a community-based study of 5,216 smokers together with information from a clinical trial on smoking cessation involving 1,073 more smokers, the team found evidence that the same variants in and around the nicotine receptor genes CHRNA5, CHRNA3, and CHRNB4 that have been linked to nicotine dependence and heavy smoking risk in the past also influence individuals' ability to quit smoking.
In particular, those with the smoking-associated haplotype stopped smoking at older ages and had more trouble quitting without smoking cessation medication. On the flip side, though, researchers found that smokers with this high-risk haplotype were three times more apt to respond to pharmacologic interventions and/or nicotine-replacement therapies.
"This study builds on our knowledge of genetic vulnerability to nicotine dependence, and will help us tailor smoking cessation strategies accordingly," National Institute on Drug Abuse Director Nora Volkow said in a statement. "It also highlights the potential value of genetic screening in helping to identify individuals early on and reduce their risk for tobacco addiction and its related negative health consequences."
Volkow was not directly involved in the study, though investigators involved in the effort received funding from several branches of the National Institutes of Health, including NIDA.
Histone variants merit more consistent nomenclature that reflects their phylogeny and, consequently, their potential functions, according to a large international group of researchers reporting in the journal Epigenetics & Chromatin.
Authors of the study, attendees at last year's European Molecular Biology Organization workshop on histone variants in Strasbourg, France, pondered the principles underlying existing histone nomenclature before coming up with their own modified histone naming and punctuation scheme. The nomenclature is intended to be logical and informative while maintaining the flexibility to include variants with uncertain phylogeny, the team explained.
"We propose … a unified nomenclature for variants of all five classes of histones that uses consistent but flexible naming conventions to produce names that are informative and readily searchable," corresponding author Steven Henikoff, with the Fred Hutchinson Cancer Research Center, and colleagues wrote. "The nomenclature builds on historical usage and incorporates phylogenetic relationships, which are strong predictors of structure and function."
An American Journal of Human Genetics study by University of Chicago and Columbia University researchers looks at the interplay between genetic variation and the expression of microRNAs and messenger RNAs.
Using cell lines generated from HapMap samples collected in Utah and Nigeria, the team not only searched for miRNAs whose expression led to lower levels of specific mRNAs, but also tracked down variants in the 3' UTR of genes that appeared to mediate miRNA binding and subsequent gene regulation, along with quantitative trait loci believed to influence miRNA expression. Over-represented amongst the apparent miRNA eQTLs were variants implicated in mRNA expression, researchers noted, as well as SNPs reported in past studies of complex human traits and diseases.
"This study extends our understanding of the genetic regulation of the transcriptome and suggests that genetic variation might underlie observed relationships between miRNAs and mRNAs more commonly than has previously been appreciated," University of Chicago hematology and oncology researcher Stephanie Huang, the study's senior author, and colleagues wrote.
By comparing expression, sequence, and inheritance patterns in three Tasmanian opium poppy varieties with high and low production of a cough suppressant and proposed anti-tumor compound called noscapine, a team based at the University of York and GlaxoSmithKline in Australia has pinned down a cluster of 10 genes that influence the production of the alkaloid. The genes, which cluster in a stretch of sequence that's more than 220,000 bases long, code for enzymes from five different enzyme classes in the noscapine-producing plant, researchers report in the early, online version of Science.
"We were amazed to find that this gene cluster encodes for almost the entire biosynthetic pathway for noscapine," senior author Ian Graham, director of the University of York's Centre for Novel Agricultural Products, said in a statement. "With this one discovery we have been able to produce an outline of the pathway and define a number of the steps involved — something that normally takes years."
Genomics In The Journals is a weekly feature pointing readers to select, recently published articles involving genomics and related research.