121 research outputs found
Assessing non-Mendelian inheritance in inherited axonopathies
PURPOSE: Inherited axonopathies (IA) are rare, clinically and genetically heterogeneous diseases that lead to length-dependent degeneration of the long axons in central (hereditary spastic paraplegia [HSP]) and peripheral (Charcot–Marie–Tooth type 2 [CMT2]) nervous systems. Mendelian high-penetrance alleles in over 100 different genes have been shown to cause IA; however, about 50% of IA cases do not receive a genetic diagnosis. A more comprehensive spectrum of causative genes and alleles is warranted, including causative and risk alleles, as well as oligogenic multilocus inheritance. METHODS: Through international collaboration, IA exome studies are beginning to be sufficiently powered to perform a pilot rare variant burden analysis. After extensive quality control, our cohort contained 343 CMT cases, 515 HSP cases, and 935 non-neurological controls. We assessed the cumulative mutational burden across disease genes, explored the evidence for multilocus inheritance, and performed an exome-wide rare variant burden analysis. RESULTS: We replicated the previously described mutational burden in a much larger cohort of CMT cases, and observed the same effect in HSP cases. We identified a preliminary risk allele for CMT in the EXOC4 gene (p value= 6.9 × 10-6, odds ratio [OR] = 2.1) and explored the possibility of multilocus inheritance in IA. CONCLUSION: Our results support the continuing emergence of complex inheritance mechanisms in historically Mendelian disorders
Room temperature aging to guarantee microbiological safety of Brazilian artisan Canastra cheese
Cheese and Fermented Milk Foods. Vol 1, Origins and Principles, 739 pp. Vol 2, Procedures and Analysis, 3rd ed, 2nd printing.
Vesicular Exocytosis of Foot-and-Mouth Disease Virus from Mammary Gland Secretory Epithelium of Infected Cows
Selenoesters in organic synthesis. 1. Conversion of mixed carboxylic acid esters to selenoesters
The pattern of release of free fatty acids from milk fat under the action of intrinsic and added lipases
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