Posts By: Periklis Makrythanasis

Long Runs of Homozygosity Are Enriched for Deleterious Variation.

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  Szpiech et al are reporting in the latest issue of AJHG their findings about the prevalence of deleterious mutations in ROH. Starting from two contradicting hypotheses, one predicting that ROH should be depleted of deleterious variants compared to the rest of the genome and a second predicting the opposite result, they studied 27 individuals […]

De novo mutations in histone-modifying genes in congenital heart disease

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Zaidi et al are reporting in Nature the identification of several de novo mutations in genes in the H3K4me pathway in patients with Congenital Heart Disease (CHD). The genes were identified after comparing the incidence of de novo mutations in 362 severe CHD cases and 264 controls by analysing exome sequencing of parent–offspring trios. After selecting for damaging […]

Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants

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Fu et al, studied exome sequencing data from 6,515 individual of European American and African American ancestry in order to define the age of Single Nucleotide Variants (SNVs) in the human genome. Using 6 different demographic models and based on a modified Out-of-Africa model, they estimated the age of all of the 1,146,601 identified SNVs. They […]

NMNAT1 mutations cause Leber congenital amaurosis

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Falk et al, Chiang et al, Perrault et al, Koenekopp et al are reporting independently in Nat Genetics the identification of NMNAT1 as cause for an autosomal recessive form Leber Congenital Amaurosis(LCA) and all individuals with NMNAT1 mutations also had macular colobomas, due to severe degeneration of the central retina. NMNAT1 is the gene linked to […]

Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.

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Emond et al are reporting in Nat Genetics the identification of DCTN4 as a modifier for P.aeruginosa infection in patients with cystic fibrosis. It is a well-established fact that the majority of patients with cystic fibrosis develop acute and chronic P.aerugonisa infections which are associated with a worse clinical outcome. The authors selected and exome […]

PSORS2 is Due to Mutations in CARD14

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Catherine Jordan et al are reporting in The American Journal of Human Genetics their study which “concludes a 17 year search for PSORS2”. PSORS2 is one of the loci identified in multiple GWAS and linkage studies as a risk locus for psoriasis and after sequencing of the genes in the identified chromosomal interval; ZNF750 was designated as […]

Evidence of non-random mutation rates suggests an evolutionary risk management strategy

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Martincorena et al are reporting in Nature evidence challenging the tenet that mutations occur randomly and then selection governs whether they are fixed or not. By comparing 34 E.coli genomes  and after excluding usual causes of difference in mutation rate (codon usage bias, mRNA-folding stability in the 5´, GC content and within-species homologous recombination)  the authors […]

Mutations in SWI/SNF complex genes are causing Coffin-Siris syndrome

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Santen et al and Tsurusaki et al are reporting in Nature Genetics that mutations in the SWItch/Sucrose NonFermenting (SWI/SNF) complex are causing Coffin-Siris syndrome. SWI/SNF has important roles in lineage specification, maintenance of stem cell pluripotency and tumorigenesis and there is evidence that it may act as an epigenetic modifier by altering chromatin structure, thereby […]

Mutations in SRCAP, Encoding SNF2-Related CREBBP Activator Protein, Cause Floating-Harbor Syndrome.

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Hood et al, are reporting in the AJHG that SRCAP is causing Floating-Harbor Syndrome. Exome sequencing in five unrelated individuals identified mutations in SRCAP ; all are tightly clustered within a small (111 codon) region of the final exon. The results were further verified by identifying mutations in 8 more patients. In all the instances […]