RESUMO
OBJECTIVE: To identify susceptibility loci for nodal osteoarthritis. METHODS: A genome screen at an average marker spacing of 9.29 cM was carried out on 558 people from 202 families, of whom 491 had nodal osteoarthritis. All genotyped people were graded for the incidence and severity of distal interphalangeal (DIP) nodes, and radiographs from 354 people were graded for joint-space narrowing (JSN) and osteophytes (OSTs). Age-regressed indices for DIP nodes, JSN and OSTs were calculated using these phenotypic data. Affected sibling pair (ASP) and quantitative trait analyses were carried out using MERLIN. RESULTS: The data analysis identified suggestive linkage to loci on chromosomes 3 (for JSN and OST), 4 (for JSN), 8 (for DIP), 11 (for radiographic osteoarthritis) and 16 (for JSN). Both the ASP and quantitative analyses identified the loci on chromosomes 4 and 11. The loci on chromosomes 3 and 16 overlap with those previously identified for large-joint osteoarthritis. Of the loci identified by the quantitative analyses with the logarithm of the odds of linkage >1.5, two were linked to more than one trait, whereas nine were linked to single traits: one for DIP, six for JSN and two for OST. CONCLUSION: The ASP and quantitative analyses of the cohort with nodal osteoarthritis suggest that multiple susceptibility loci for osteoarthritis influence the traits, which combine to form the osteoarthritis phenotype, and that these loci may not act exclusively on the joints of the hand.
Assuntos
Predisposição Genética para Doença , Osteoartrite/genética , Locos de Características Quantitativas , Estudos de Coortes , Feminino , Articulações dos Dedos/diagnóstico por imagem , Articulações dos Dedos/patologia , Ligação Genética , Genoma Humano , Genótipo , Humanos , Masculino , Repetições de Microssatélites , Osteoartrite/diagnóstico por imagem , Osteoartrite/patologia , Fenótipo , Radiografia , Índice de Gravidade de DoençaAssuntos
Proteoglicanas de Sulfatos de Condroitina/genética , Cromossomos Humanos Par 15 , Proteínas da Matriz Extracelular/genética , Lectinas Tipo C/genética , Osteocondrodisplasias/genética , Agrecanas , Ligação Genética , Predisposição Genética para Doença , Humanos , Linhagem , Polimorfismo de Nucleotídeo ÚnicoRESUMO
We have investigated a family with an autosomal dominant form of spondyloepiphyseal dysplasia (SED) characterised by short stature and severe premature degenerative arthropathy. Previous studies have excluded linkage between this condition and the locus for the type II collagen gene. Here we report the identification of linkage between this disorder and a locus on the long arm of chromosome 15 between markers D15S979 and D15S1004. According to current linkage maps and sequence data, this locus includes that of the aggrecan gene (AGC1). Our linkage data from the SED family show, however, that AGC1 maps to a locus that is proximal to D15S979. This proximal location for AGC1 is further supported by linkage data from a second family with an autosomal recessive form of multiple epiphyseal dysplasia that also maps to the SED locus. In both families AGC1 is therefore excluded as a candidate gene.
Assuntos
Cromossomos Humanos Par 15/genética , Proteínas da Matriz Extracelular , Osteocondrodisplasias/genética , Agrecanas , Mapeamento Cromossômico , Saúde da Família , Feminino , Ligação Genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Lectinas Tipo C , Masculino , Repetições de Microssatélites , Osteocondrodisplasias/patologia , Linhagem , Fenótipo , Proteoglicanas/genéticaRESUMO
The reverse transcriptase polymerase chain reaction (RT-PCR) is a sensitive technique that can detect prostate-specific messenger RNA in circulating blood. Many authors have studied the potential of RT-PCR as a staging technique in prostate cancer (PC). Clinical sensitivity and in some cases specificity has been disappointing. Few authors have been able to correlate RT-PCR result with patient stage. We have compared the results of using two different RT-PCR protocols with different sensitivities on blood samples from prostate cancer patients. An 80-amplification-cycle nested primer RT-PCR assay had a detection limit of 10 prostate cells and a 50-cycle RT-PCR could detect 20 cells in 5 ml blood. The 80-cycle assay detected prostate mRNA in four of 10 female samples, whereas the 50-cycle assay detected it in none. There was little difference in the assays' ability to detect prostate mRNA in advanced PC patients. The 50-cycle assay could differentiate between hormone-escaped, stable hormone-treated and untreated localized PC patients, whereas the 80-cycle assay could not. Each blood sample must be assayed several times with RT-PCR to avoid false-negative results and, if this is done, assay specificity can be increased with little effect on clinical sensitivity.
