Biology subjects

Pollock, A.

Publications and source records attributed to Pollock, A..

3 recordsLinked to original sources

bioRxiv2018

Molecular Screening of Familial Hypercholesterolemia in the Icelandic Population

Familial hypercholesterolemia (FH) is a monogenic disease characterized by a lifelong exposure to high LDL-C levels that can lead to early onset coronary heart disease (CHD). The main causes of FH identified to date include loss-of-function mutations in LDLR or APOB, or gain-of-function mutations in PCSK9. Early diagnosis and genetic testing of FH suspects is critical for improved prognosis of affected individuals as lipid lowering treatments are effective in preventing CHD related morbidity and mortality. In the present manuscript, we developed a comprehensive next generation sequencing (NGS) panel which we applied on two different resources of FH in the Icelandic population: 62 subjects from 23 FH families with known or unknown culprit mutations, and a population-based sampling of 315 subjects selected for total cholesterol levels above the 95th percentile cut-point. The application of the NGS panel revealed significant diagnostic yields in identifying pathogenic LDLR mutations in both family and population-based genetic testing.

genetics↗

bioRxiv2018

MicroRNA miR-7 and miR-17-92 in POMC neurons are associated with sex-specific regulation of diet-induced obesity

Proopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) in mammalian hypothalamus play important roles in regulating appetite, energy expenditure, and glucose and fat metabolisms. Diet-induced obesity often show sex-specific difference. But the underlying mechanisms remain unclear. Here we show that microRNA (miRNA) miR-7 and miR-17-92 are expressed in the mouse ARC, and mostly in POMC neurons. Knockdown of miR-7 and knockout of miR-17-92 specifically in POMC neurons aggravate diet-induced obesity only in females and males, respectively. Moreover, gene expression profile analysis identifies sex-differential genes in male and female ARCs in wildtype adult mice. Interestingly, these genes that normally show low-expression in the female and male ARCs display upregulated expression in female miR-7 knockdown and male miR-17-92 knockout mice, respectively. Our results demonstrate an important role of miRNAs in regulating sex-specific diet-induced obesity, likely through modulating expression of target genes that show sex-differential expression in the ARC of hypothalamus.

neuroscience↗

bioRxiv2018

Comprehensive Genetic Testing for Female and Male Infertility Using Next Generation Sequencing

ObjectiveTo develop a comprehensive genetic test for female and male infertility in support of medical decisions during assisted reproductive technology (ART) protocols.\n\nDesignRetrospective analysis of results from 118 DNA samples with known variants in loci representative of female and male infertility.\n\nInterventions(s)None\n\nMain Outcome Measure(s)Next-Generation Sequencing (NGS) of 87 genes including promoters, 5 and 3 untranslated regions, exons and selected introns. In addition, sex chromosome aneuploidies and Y chromosome microdeletions are analyzed concomitantly using the same panel.\n\nResultsAnalytical accuracy was >99%, with >98% sensitivity for Single Nucleotide Variants (SNVs) and >91% sensitivity for insertions/deletions (indels). Clinical sensitivity was assessed with samples containing variants representative of male and female infertility, and it was 100% for SNVs/indels, CFTR IVS8-5T variants, sex chromosome aneuploidies and Copy Number Variants (CNVs), and >93% for Y chromosome microdeletions. Cost analysis comparing the NGS assay with standard, multiple analysis approach, shows potential savings of $2723 per case. Conclusion: A single, comprehensive, NGS panel can simplify the ordering process for healthcare providers, reduce turnaround time, and lower the overall cost of testing for genetic assessment of infertility in females and males, while maintaining accuracy.

genomics↗