[Preliminary linkage analysis on autosomal dominant microphthalmia with 12 microsatellite markers].

Department of Medical Genetics, Zhejiang University Medical School, Hangzhou 310006.
Shi yan sheng wu xue bao 05/2004; 37(2):85-90.
Source: PubMed


In this preliminary study a Chinese autosomal dominant microphthalmia family were investigated and the linkage analyses were performed with six previously reported loci (CHX10, MITF, RX, MCOP, NNO1, NNO2) and six microsatellite markers on chromosome 11 as well. The allelic polymorphisms of those microsatellite markers were identified by using polymerase chain reaction, polyacrylamide gel electrophoresis and silver-staining techniques. The LOD scores between microsatellite markers and the disease were obtained by using MLINK software. Our results showed that the linkage between the microphthalmia in this family with the 6 known loci could be excluded, indicating that the defect gene in this microphthalmia family was probably distinct from those of previously reported microphthalmia families.

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    • "The disease pattern of the pedigree is nonsyndromic. The karyotype in this pedigree was normal (46, XX.) (Yu et al. 2004), and our prophase work (Yin et al. 2006; Yu et al.2004) have excluded the linkage of microphthalmia in this pedigree with the reported eight candidate loci (MITF, CHX10, NNO1, NNO2, PAX6, RX, MCOP and SOX2) (Bessant et al. 1998; Ferda Percin et al. 2000; Hagstrom et al. 2005; Hanson 2003; Morle et al. 2000; Othman et al. 1998; Tassabehji et al. 1994; Voronina et al. 2004). In order to further identify the gene responsible for this Chinese microphthalmia family, we performed a whole-genome scan analysis by using 382 micro-satellite markers in the 22 pairs of autosomes. "
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    ABSTRACT: Microphthalmia is a clinically and genetically heterogeneous disorder of eye development. The genetic basis of nonsyndromic microphthalmia is not yet fully understood. Previous studies indicated that disease pedigrees from different genetic backgrounds could be attributed to completely different gene loci. To investigate the etiology in a large autosomal-dominant inherited simple microphthalmia (nanophthalmia) pedigree, which is the first genetically analyzed Chinese microphthalmia pedigree, we performed a whole-genome scan using 382 micro-satellite DNA markers after the exclusion of reported candidates associated with microphthalmia. Strong evidence indicated that microphthalmia in this family was mapped to an unreported new locus on chromosome 2q. A significantly positive two-point LOD score was obtained with a maximum 3.290 at a recombination fraction of 0.00 for marker D2S2265. Subsequent haplotype analysis and recombination data further confined the disease-causing gene to a 15-cM interval between D2S1890 and D2S347 on 2q11-14. Our results further underlined the degree of heterogeneity in microphthalmia from Chinese background and localized a novel gene which regulates eye embryogenesis.
    Full-text · Article · Feb 2008 · Human Genetics
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    ABSTRACT: Congenital microphthalmia is a developmental ocular disorder and might be caused by the mutations in the genes involved in eye development. To uncover the genetic cause in a six-generation Chinese pedigree with autosomal dominant congenital microphthalmia, we performed genescan and linkage analysis in this family. Fourteen microsatellite markers on chromosomes 3, 11, 14 and 15 were selected as genetic markers according to the five previously reported loci associated with microphthalmia (MITF, SOX2, PAX6, MCOP and NNO2). The genomic DNA of each member in the pedigree was amplified with 14 pairs of fluorescence labeled primers. Genome screening and genotyping were conducted on ABI377 DNA sequencer and linkage analysis was performed with Linkage software package. All two-point LOD scores of linkage analysis between the suggested disease genes and microsatellite markers were <−2, which indicated that none of the five genes were responsible for microphthalmia in this Chinese family. Microphthalmia in this family may be caused by mutation in a new gene which is essential in eye development.
    No preview · Article · Nov 2006 · Chinese Science Bulletin