Showing papers by "Jared C. Roach published in 2010"

Analysis of genetic inheritance in a family quartet by whole-genome sequencing

Abstract: We analyzed the whole-genome sequences of a family of four, consisting of two siblings and their parents. Family-based sequencing allowed us to delineate recombination sites precisely, identify 70% of the sequencing errors (resulting in > 99.999% accuracy), and identify very rare single-nucleotide polymorphisms. We also directly estimated a human intergeneration mutation rate of approximately 1.1 x 10(-8) per position per haploid genome. Both offspring in this family have two recessive disorders: Miller syndrome, for which the gene was concurrently identified, and primary ciliary dyskinesia, for which causative genes have been previously identified. Family-based genome analysis enabled us to narrow the candidate genes for both of these Mendelian disorders to only four. Our results demonstrate the value of complete genome sequencing in families.

The association between the PTPN22 1858C>T variant and type 1 diabetes depends on HLA risk and GAD65 autoantibodies.

Abstract: The single nucleotide polymorphism 1858C> T in the PTPN22 gene is associated with type 1 diabetes (T1D) in several populations Earlier reports have suggested that the association may be modified by human leukocyte antigen (HLA), as well as by islet autoantibodies In a large case-control study of Swedish incident T1D patients and controls, 0-34 years of age, we tested whether the odds ratio (OR) measure of association was dependent on HLA or autoantibodies against the islet autoantigens glutamic acid decarboxylase 65 kDa autoantibodies (GADA), insulin, islet antigen-2, or islet cell The association between the carrier status of 1858C> T allele in PTPN22 (PTPN22(CT + TT)) and T1D was modified by HLA In addition, in GADA-positive T1D, the OR was 283 (200, 399), whereas in GADA-negative T1D, the OR was 141 (098, 204) (P for comparison = 0007) The OR of association between PTPN22(CT + TT) and GADA-positive T1D declined with increasing HLA-risk category from 612 to 154 (P = 0003); no such change was detected in GADA-negative T1D (P = 0722) (P for comparison = 0001) However, the absolute difference in risk between PTPN22(CC) and PTPN22(CT + TT) subjects with high-risk HLA was five times higher than that for subjects with low-risk HLA We hypothesize that the altered T-cell function because of the PTPN22(1858C> T) polymorphism is exclusively associated with GADA-positive T1D at diagnosis Genes and Immunity (2010) 11, 406-415; doi: 101038/gene201012; published online 6 May 2010 (Less)