RESUMO
Fanconi anemia (FA) is a genetically heterogeneous disease with at least eight genes on the basis of complementation groups (FAA to FAH). The analysis of the FAA gene in patients suggested the existence of deletions, none of which have thus far been characterized at the genomic level. A detailed restriction map of the FAA gene with the fine localization of its 43 exons is reported in this paper. We also describe the first two genomic deletions, one of 5.0 kb and another of at least 120 kb. The former was likely the result of a recombination between related Alu sequences. Since these interspersed repeats could generate deletions and insertions by mispairing, rearrangements of this gene are a possibility in those FA families in which FAA mutations have not been identified.
Assuntos
Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Anemia de Fanconi/genética , Proteínas Nucleares , Proteínas/genética , Deleção de Sequência/genética , Sequência de Bases , Éxons/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi , Humanos , Íntrons/genética , Dados de Sequência Molecular , Recombinação Genética/genética , Sequências Repetitivas de Ácido Nucleico/genética , Mapeamento por Restrição , Análise de Sequência de DNARESUMO
The detection of carrier status in female relatives of Duchenne/Becker muscular dystrophy patients is not always possible and this poses a problem in genetic counseling. We have developed a simple method that can be used in families in which affected males are characterized by the presence of a deletion within the dystrophin gene. PCR fragments, corresponding to the deleted regions are used as fluorescent probes for hybridization of peripheral lymphocytes nuclei of female relatives. The results obtained clearly demonstrate the feasibility of this method for detecting female DMD/BMD carriers.
Assuntos
Distrofina/genética , Triagem de Portadores Genéticos/métodos , Hibridização in Situ Fluorescente/métodos , Distrofias Musculares/genética , Deleção de Sequência , Feminino , Humanos , Masculino , LinhagemRESUMO
Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant condition consisting of congenital dysplasia of the eyelids with a reduced horizontal diameter of the palpebral fissures, droopy eyelids and epicanthus inversus. Two clinical entities have been described: type I and type II. The former is distinguished by female infertility, whereas the latter presents without other symptoms. Both type I and type II were recently mapped on the long arm of chromosome 3 (3q22-q23), suggesting a common gene may be affected. The centromeric and the telomeric limits of this region are well defined between loci D3S1316 and D3S1615, which reside approximately 5 cM apart. Here, we present the construction of a YAC contig spanning the entire BPES locus using 17 polymorphic markers, 2 STS and 28 ESTs. This region of approximately 5 Mb was covered by 31 YACs, and was supported by detailed FISH analysis. In addition, we have precisely mapped the propionyl-CoA carboxylase beta polypeptide (PCCB), the gene mutated in propionic acidemia, within this contig. Apart from providing a framework for the identification of the BPES gene, this contig will also be useful for the future identification of defects and genes mapped to this region, and for developing template resources for genomic sequencing.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Blefarofimose/genética , Blefaroptose/genética , Mapeamento Cromossômico , Cromossomos Artificiais de Levedura/genética , Cromossomos Humanos Par 3/ultraestrutura , Propionatos/sangue , Carboxiliases/genética , Primers do DNA , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Marcadores Genéticos , Humanos , Hibridização in Situ Fluorescente , Infertilidade Feminina/genética , Metilmalonil-CoA Descarboxilase , Reação em Cadeia da Polimerase , Polimorfismo Genético , Sequências Repetitivas de Ácido Nucleico , Sitios de Sequências Rotuladas , SíndromeRESUMO
A new genetic disorder (Hyperferritinemia and Cataract Syndrome) characterized by a combination of high serum ferritin level and congenital bilateral nuclear cataract has been recently described. This disease is transmitted as autosomal dominant trait and is due to mutations in the ferritin L gene (FTL). FTL gene has been localized to 19q13.3-qter by somatic cell hybrids. In this work we present the precise mapping of FTL gene on chromosome 19q13.3 using in situ fluorescence hybridization.
Assuntos
Bandeamento Cromossômico , Cromossomos Humanos Par 19 , Ferritinas/genética , Apoferritinas , Catarata/genética , Ferritinas/sangue , Genes Dominantes , Humanos , Hibridização in Situ Fluorescente , SíndromeRESUMO
Two patients were referred because of oligospermia and azospermia, respectively. Karyotypic analysis revealed two mosaic-YY males carrying asymmetric Y chromosomes. To our knowledge, no instance of double unequal Y chromosomes has been reported so far in human males. Results of fluorescent in situ hybridization (FISH) studies in spermatozoa from one of these patients revealed a significantly high number of hyperaploid spermatozoa.