Assuntos
Cromossomos Humanos Par 19 , Distrofia Miotônica/genética , Polimorfismo Genético , Sequências Repetitivas de Ácido Nucleico , Alelos , Sequência de Bases , DNA/genética , Frequência do Gene , Marcadores Genéticos , Humanos , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos/genéticaRESUMO
We identified a large kindred that shows classical myotonic dystrophy (MyD), together with hereditary motor and sensory neuropathy (HMSN) in some individuals, and HMSN alone in others. A previous study of this family has shown cosegregation of the MyD and HMSN phenotypes with the Lutheran and secretor loci in some branches of the family, indicating linkage to chromosome 19. We reanalyzed this family with 2 recombinant DNA marker systems from the ApoC2 locus on chromosome 19. Our results demonstrate that all affected individuals have inherited a unique ApoC2 haplotype that was not found in their clinically and electrophysiologically normal sibs. We also obtained evidence against involvement of the HMSN I locus on chromosome 17. In this family, a moderately severe neuropathy may be the only clinical sign of MyD for many years. Our results are consistent with an unusual neuropathic mutation at the MyD gene. However, involvement of 2 closely linked genes (1 for MyD and the other for HMSN) can also explain our findings.
Assuntos
Cromossomos Humanos Par 17 , Cromossomos Humanos Par 19 , Ligação Genética , Neuropatia Hereditária Motora e Sensorial/genética , Distrofia Miotônica/genética , Adolescente , Adulto , Criança , DNA/análise , Eletromiografia , Feminino , Neuropatia Hereditária Motora e Sensorial/complicações , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/complicações , Linhagem , Exame FísicoRESUMO
Employing 16 polymorphic DNA markers as well as the chromosome 19 centromere heteromorphism, we have performed a genetic linkage study in 26 families with myotonic dystrophy. Fourteen of these markers had been assigned previously to one of five different intervals of the 19cen-19q13.2 segment by using somatic cell hybrids. For the long arm of chromosome 19, a genetic map that encompasses 9 polymorphic markers and the DM gene has been constructed. Our studies indicate that the DM and CKMM genes map distal to the ApoC2-ApoE gene cluster and to the anonymous polymorphic markers D19S15 and D19S16, but proximal to the D19S22 marker. The orientation of DM and CKMM remains to be determined.
Assuntos
Cromossomos Humanos Par 19 , Ligação Genética , Distrofias Musculares/genética , Mapeamento Cromossômico , Troca Genética , Análise Mutacional de DNA , Feminino , Marcadores Genéticos , Humanos , Masculino , Polimorfismo de Fragmento de Restrição , Recombinação GenéticaRESUMO
The localization to 19q of the gene causing myotonic dystrophy (DM) has been defined more precisely by refinement of the physical location of several linked markers. A somatic cell hybrid mapping panel from cells with t(1;19), t(12;19), and t(X;19) translocation products was constructed to define five different intervals across 19q. In addition, we have derived a series of cell hybrids by irradiation of a der(19)-only hybrid to further subdivide the cen-q13.1 region. Using an array of 36 cloned genes, anonymous DNAs, and enzyme markers, we have tested the location of the panel breakpoints and refined the regional assignment of several of these markers. All markers tightly linked to DM are localized mainly within 19q13.2, thus suggesting that the DM gene is also close to this region.
Assuntos
Cromossomos Humanos Par 19/ultraestrutura , Distrofia Miotônica/genética , Animais , Mapeamento Cromossômico , Cricetinae , Sondas de DNA , Marcadores Genéticos , Humanos , Células Híbridas , Camundongos , Hibridização de Ácido Nucleico , Homologia de Sequência do Ácido Nucleico , Especificidade da EspécieRESUMO
We have studied genetic linkage between the gene for creatine kinase muscle type (CKMM) and the gene for myotonic dystrophy (DM). In a panel of 65 myotonic dystrophy families from Canada and the Netherlands, a maximum lod score (Zmax) of 22.8 at a recombination frequency (theta) of 0.03 was obtained. Tight linkage was also demonstrated for CKMM and the gene for apolipoprotein C2 (ApoC2). This establishes CKMM as a useful marker for myotonic dystrophy.
Assuntos
Cromossomos Humanos Par 19 , Creatina Quinase/genética , Ligação Genética , Distrofia Miotônica/genética , Apolipoproteína C-II , Apolipoproteínas C/genética , Frequência do Gene , Marcadores Genéticos , Humanos , Isoenzimas , Recombinação GenéticaRESUMO
We have cloned and characterized two distinct types of alphoid DNA elements. Probe pG-Xba 11/340 was obtained by random cloning of human satellite DNA and contains two basic units with overall 88% homology to the 171-bp consensus alphoid sequence. pG-Xba 11/340-like elements are represented about 2,000-4,000 times in the haploid genome and, by in situ hybridization, are found exclusively at the primary constrictions of chromosomes 4 and 9. Probe pG-A16 was cloned from a chromosome 19-specific cosmid library and represents a 2.25-kb higher-order DNA element which is present at roughly 75-150 copies per haploid genome and which hybridizes to the centromeres of chromosomes 5 and 19. Using the pG-A16 probe, further genetic and physical dissection of the central area of chromosome 19 can be envisaged.