Non HFE related hereditary haemochromatosis.

Hereditary hemochromatosis (HH) is manifested as iron overload in different organs due to homozygosity of a single autosomal mutation. Two different mutations C282Y and H63D in the HFE gene have been associated with hereditary hemochromatosis cases. This disease is seen in northern european populations, but in India it is a rare disease. We report a young male with severe abnormalty of liver functions due to Non HFE related Hereditary Hemochromatosis.

Joint variant and de novo mutation identification on pedigrees from high-throughput sequencing data.

The analysis of whole-genome or exome sequencing data from trios and pedigrees has been successfully applied to the identification of disease-causing mutations. However, most methods used to identify and genotype genetic variants from next-generation sequencing data ignore the relationships between samples, resulting in significant Mendelian errors, false positives and negatives. Here we present a Bayesian network framework that jointly analyzes data from all members of a pedigree simultaneously using Mendelian segregation priors, yet providing the ability to detect de novo mutations in offspring, and is scalable to large pedigrees. We evaluated our method by simulations and analysis of whole-genome sequencing (WGS) data from a 17-individual, 3-generation CEPH pedigree sequenced to 50× average depth. Compared with singleton calling, our family caller produced more high-quality variants and eliminated spurious calls as judged by common quality metrics such as Ti/Tv, Het/Hom ratios, and dbSNP/SNP array data concordance, and by comparing to ground truth variant sets available for this sample. We identify all previously validated de novo mutations in NA12878, concurrent with a 7× precision improvement. Our results show that our method is scalable to large genomics and human disease studies.