Gametic selection during fertilization or the effects of specific genotypes on the viability of embryos may cause a skewed transmission of chromosomes to surviving offspring. A recent analysis of transmission distortion in humans reported significant excess sharing among full siblings. Dizygotic (DZ) twin pairs are a special case of the simultaneous survival of two genotypes, and there have bee...

Sequencing family DNA samples provides an attractive alternative to population based designs to identify rare variants associated with human disease due to the enrichment of causal variants in pedigrees. Previous studies showed that genotype calling accuracy can be improved by modeling family relatedness compared to standard calling algorithms. Current family-based variant calling methods use s...

Multipoint linkage analysis is a powerful tool to localize susceptibility genes for complex diseases. However, the conventional lod score method relies critically on the correct specification of mode of inheritance for accurate estimation of gene position. On the other hand, allele-sharing methods, as currently practiced, are designed to test the null hypothesis of no linkage rather than estima...

Sharing a Common Pathogenic Pathway? To the Editor: The paper by Urbich et al1 suggests that the CD40 pathway is involved in the vascular restenotic process. The immuneinflammatory reaction plays a critical role in atherosclerosis. In particular, the ligand for CD40 (CD40L) is involved in inflammation, thrombosis, and restenosis during progression of atherosclerosis, as discussed by Andre’ et a...

OBJECTIVE To clarify the mode of genetic contribution of the HLA-DR shared epitope (SE) to the pathogenesis of familial cases of Japanese rheumatoid arthritis (RA). METHODS Fifty-three unrelated Japanese RA families that had more than 2 affected sibs were selected. The HLA-DR shared epitope typing was carried out by the PCR method and PCR-SSCP (single stranded DNA conformation polymorphism) m...

OBJECTIVE To assess whether combined evidence shows the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) C1858T polymorphism and autoimmune diseases, and to summarize the effect size of the polymorphism associated with susceptibility of autoimmune diseases. METHODS We surveyed studies on the PTPN22 C1858T polymorphism and autoimmune diseases using comprehensive Me...

Although a few hundred single nucleotide polymorphisms (SNPs) suffice to infer close familial relationships, high density genome-wide SNP data make possible the inference of more distant relationships such as 2(nd) to 9(th) cousinships. In order to characterize the relationship between genetic similarity and degree of kinship given a timeframe of 100-300 years, we analyzed the sharing of DNA in...

20 The rate at which human genomes mutate is a central biological parameter that 21 has many implications for our ability to understand demographic and evolutionary 22 phenomena. We present a method for inferring mutation and gene conversion rates 23 using the number of sequence differences observed in identical-by-descent (IBD) 24 segments together with a reconstructed model of recent populati...

A novel computational method for detecting identical-by-descent (IBD) chromosomal segments between sequenced genomes is presented. It utilizes the distribution patterns of very rare genetic variants (vrGVs), which have minor allele frequencies <0.2%. Contrary to the existing probabilistic approaches our method is rather deterministic, because it considers a group of very rare events which canno...

Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn's di...