Linkage analysis of chromosome 2q in osteoarthritis.

Background: In independent linkage studies chromosome 2q11-q24 and chromosome 2q23-35 have previously been implicated as regions potentially harbouring susceptibility loci for osteoarthritis (OA).

Objective: To test chromosome 2q for linkage to idiopathic osteoarthritis.

Methods: Using a cohort of 481 OA families that each contained at least one affected sibling pair with severe end-stage disease (ascertained by hip or knee joint replacement surgery), we conducted a linkage analysis of chromosome 2q using 16 polymorphic microsatellite markers at an average spacing of one marker every 8.

Linkage analysis of candidate genes as susceptibility loci for osteoarthritis-suggestive linkage of COL9A1 to female hip osteoarthritis.

Objective: To examine 11 candidate genes as susceptibility loci for osteoarthritis (OA).

Methods: A total of 481 families have been ascertained in which at least two siblings have had joint replacement surgery of the hip, or knee, or hip and knee for idiopathic OA. Each candidate gene was targeted using one or more intragenic or closely linked microsatellite marker.

Surnames and the Y chromosome.

A randomly ascertained sample of males with the surname "Sykes" was typed with four Y-chromosome microsatellites. Almost half the sample shared the same Y-chromosome haplotype, which has not been observed in control samples either from the same geographic region or from the United Kingdom as a whole. This points to a single surname founder for extant Sykes males, even though written sources had predicted multiple origins.

Osteoarthritis-susceptibility locus on chromosome 11q, detected by linkage.

We present a two-stage genomewide scan for osteoarthritis-susceptibility loci, using 481 families that each contain at least one affected sibling pair. The first stage, with 272 microsatellite markers and 297 families, involved a sparse map covering 23 chromosomes at intervals of approximately 15 cM. Sixteen markers that showed evidence of linkage at nominal P View Article and Find Full Text PDF

European Y-chromosomal lineages in Polynesians: a contrast to the population structure revealed by mtDNA.

We have used Y-chromosomal polymorphisms to trace paternal lineages in Polynesians by use of samples previously typed for mtDNA variants. A genealogical approach utilizing hierarchical analysis of eight rare-event biallelic polymorphisms, seven microsatellite loci, and internal structural analysis of the hypervariable minisatellite, MSY1, has been used to define three major paternal-lineage clusters in Polynesians. Two of these clusters, both defined by novel MSY1 modular structures and representing 55% of the Polynesians studied, are also found in coastal Papua New Guinea.

Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II).

Ehlers-Danlos syndrome (EDS) is a group of heritable disorders of connective tissue with skin, ligaments and blood vessels being the main sites affected. The commonest variant (EDS II) exhibits an autosomal dominant mode of inheritance and is characterized by joint hypermobility, cigarette paper scars, lax skin and excessive bruising. As yet no gene has been linked to EDS II, nor has linkage been established to a specific region of the genome.

Differential allelic expression of the type II collagen gene (COL2A1) in osteoarthritic cartilage.

Osteoarthritis (OA) is a common debilitating disease resulting from the degeneration of articular cartilage. The major protein of cartilage is type II collagen, which is encoded by the COL2A1 gene. Mutations at this locus have been discovered in several individuals with inherited disorders of cartilage.

Sibling pair analysis shows no linkage of generalized osteoarthritis to the loci encoding type II collagen, cartilage link protein or cartilage matrix protein.

Generalized OA (GOA) is a well-characterized subset of primary OA which is strongly associated with the occurrence of Heberden's nodes. Using gene-specific highly polymorphic markers and affected sib pair (ASP) analyses, we have investigated genetic linkage between GOA and three cartilage matrix genes: COL2A1 which encodes type II collagen; CRTL1 which encodes the cartilage link protein and CRTM which encodes the cartilage matrix protein. The analyses showed no linkage between GOA and the three genes in the 38 sib pairs examined.

Exclusion of the cartilage link protein and the cartilage matrix protein genes as the mutant loci in several heritable chondrodysplasias.

The chondrodysplasias are characterised by the abnormal development of articulating joints and bone. Mutations in the COL2A1 and COL10A1 genes, which encode the cartilage collagens type II and type X, have been identified in a variety of inherited chondrodysplasias. However, both genes have also been excluded as the mutant loci in several chondrodysplasia pedigrees, indicating the existence of at least one other chondrodysplasia locus.

Mutation screening by a combination of biotin-SSCP and direct sequencing.

We have developed a mutation detection strategy that combines single strand conformational polymorphism (SSCP) analysis of one strand of a double-stranded amplification product with direct sequencing of the other. Using this strategy, which we find economical of both time and resources, we have identified a G to A transition, which substitutes a serine for glycine residue at position 862 in the major helix of the alpha 1 chain of Type I collagen. We use this mutation, which causes a lethal form of osteogenesis imperfecta, to illustrate the technique.