RESUMO
Progressive pseudorheumatoid dysplasia is an autosomal recessive skeletal dysplasia with radiographic changes in the spine similar to Spondyleopiphyseal dysplasia tarda and clinical, though not radiographic resemblance to rheumatoid arthritis. About two-thirds of the reported patients are of Arabic and Mediterranean origin which reflects the relative high incidence in this population. We performed homozygosity mapping utilising the DNA pooling approach to map progressive pseudorheumatoid dysplasia to a chromosomal region on the long arm of chromosome 6. We examined a possible candidate gene in the same region of linkage, namely COL10A1, for alterations in this disorder. We did not identify any mutations in our family, but did not totally exclude COL10A1 gene from being the disease-causing gene.
Assuntos
Cromossomos Humanos Par 6 , Colágeno/genética , Osteocondrodisplasias/genética , Sequência de Bases , Mapeamento Cromossômico , Primers do DNA , Feminino , Ligação Genética , Homozigoto , Humanos , Masculino , LinhagemRESUMO
SNPs (Single-Nucleotide Polymorphisms), the most common DNA variant in humans, represent a valuable resource for the genetic analysis of cancer and other illnesses. These markers may be used in a variety of ways to investigate the genetic underpinnings of disease. In gene-based studies, the correlations between allelic variants of genes of interest and particular disease states are assessed. An extensive collection of SNP markers may enable entire molecular pathways regulating cell metabolism, growth, or differentiation to be analyzed by this approach. In addition, high-resolution genetic maps based on SNPs will greatly facilitate linkage analysis and positional cloning. The National Cancer Institute's CGAP-GAI (Cancer Genome Anatomy Project Genetic Annotation Initiative) group has identified 10,243 SNPs by examining publicly available EST (Expressed Sequence Tag) chromatograms. More than 6800 of these polymorphisms have been placed on expression-based integrated genetic/physical maps. In addition to a set of comprehensive SNP maps, we have produced maps containing single nucleotide polymorphisms in genes expressed in breast, colon, kidney, liver, lung, or prostate tissue. The integrated maps, a SNP search engine, and a Java-based tool for viewing candidate SNPs in the context of EST assemblies can be accessed via the CGAP-GAI web site (http://cgap.nci.nih.gov/GAI/). Our SNP detection tools are available to the public for noncommercial use.
Assuntos
Mapeamento Cromossômico/métodos , Expressão Gênica , Projeto Genoma Humano , Neoplasias/genética , Mapeamento Físico do Cromossomo/métodos , Polimorfismo de Nucleotídeo Único/genética , Mapeamento Cromossômico/tendências , Bases de Dados Factuais , Biblioteca Gênica , Ligação Genética , Humanos , Armazenamento e Recuperação da Informação , Internet , Mapeamento Físico do Cromossomo/tendências , Reprodutibilidade dos Testes , SoftwareRESUMO
We investigated 116 Italian atopic families (560 individuals) for linkage with 13 DNA markers on chromosome 12. All the subjects were phenotyped for asthma, total serum IgE, bronchial hyperresponsiveness, skin-prick positivity to common aeroallergens, and atopy. A relative location map of the markers was prepared from Centre d'Etude du Polymorphisme Humain families. Affected sib pair multipoint linkage methods were used to perform the statistical analyses. We report suggestive linkage for asthma with markers on chromosome 12. The region of interest centers around marker D12S390 (maximum logarithm of odds [mlod] = 2.81; p = 0.003). These results provide additional support that asthma susceptibility factors are located on chromosome 12q.
Assuntos
Asma/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 12 , Marcadores Genéticos/genética , Hipersensibilidade Respiratória/genética , Adulto , Hiper-Reatividade Brônquica/genética , Criança , Feminino , Predisposição Genética para Doença/genética , Humanos , Itália , Masculino , FenótipoRESUMO
We examined the long arm XY pseudoautosomal region for linkage to asthma, serum IgE, and bronchial hyperresponsiveness. In 57 Caucasian families multipoint nonparametric analyses provide evidence for linkage between DXYS154 and bronchial hyperresponsiveness (P = 0.000057) or asthma (P = 0.00065). This genomic region is approximately 320 kb in size and contains the interleukin-9 receptor gene. These results suggest that a gene controlling asthma and bronchial hyperresponsiveness maybe located in this region and that the interleukin-9 receptor is a potential candidate.