RESUMO
We have evaluated the structure of the CGG repeat within the FMR1 gene of an Asian population and found the most common size of the repeat to be 29 and 30 with a minor population of 36 repeats. We have isolated and sequenced DNA containing the 36 repeats and found the basis sequence to be (CGG)9AGG(CGG)9AGG-(CGG)6AGG(CGG)9; with a (CGG)6)AGG insertion, designated as 9A9A6A9. Of 144 Asian chromosomes, 11 (8%) had sequences with this insertion. Six different variations of the basic sequence were observed in the population: 9A9A6A2A9, 9A9A6A11, 9A9A16, 9A9A15, 8A9A6A6A9, and 11A6A6A9. All but one of the chromosomes with the insertion had the haplotype of DXS548/ FRAXAC1: 194/D suggesting that the sequences with the 6A insertion arose from a single ancestral allele. We have not observed the insertion in the FMR1 gene of Caucasians or Native Americans. The (CGG)6AGG insertion may be unique to Asians.
Assuntos
Povo Asiático/genética , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA/genética , Repetições de Trinucleotídeos , Alelos , Evolução Molecular , Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil/etnologia , Síndrome do Cromossomo X Frágil/genética , Humanos , Indígenas Norte-Americanos/genética , Masculino , Noroeste dos Estados Unidos , Análise de Sequência de DNA , População Branca/genéticaRESUMO
We studied four variable number of tandem repeat (VNTR) loci (D4S139, D10S28, D17S74, and D17S79) in five ethnic populations from the Seattle metropolitan area. DNA samples purified from randomly chosen individuals were digested with Hae III or Hinf I and probed with pH30, for D4S139; TBQ7 for D10S28; pCMM86 for D17S74 and pAC256 for D17S79. The allele frequencies, expected Hardy-Weinberg values, observed heterozygosities and genetic distances among the populations were obtained for all these loci. D4S139 restriction fragment lengths (RFLs) varied in size from 1.4 to 22 kilobase pairs (kbp). The observed heterozygosities (H) varied from 84% in Native American populations to 94% among Blacks. D10S28 RFLs varied in size from 650 base pairs (bp) to 10.1 kbp. H varied from 90% in Native Americans to 96% in Caucasians and Hispanics. D17S74 RFLs varied in size from 782 bp to 9.3 kbp. H varied from 87% in Asians to 92% among Blacks. D17S79 RFLs varied in size from 400 bp to 3 kbp. H varied from 87% in Hispanics to 95% in the Black population. The frequencies of genotypes of the loci conformed to Hardy-Weinberg equilibrium with the exception of the D17S79 in Hispanics and Native Americans. The genetic distances between the populations were also determined.
Assuntos
Etnicidade/genética , Repetições Minissatélites , Grupos Raciais/genética , Alelos , Povo Asiático/genética , População Negra/genética , Frequência do Gene , Marcadores Genéticos , Variação Genética , Hispânico ou Latino/genética , Humanos , Indígenas Norte-Americanos/genética , Modelos Genéticos , Washington , População Branca/genéticaRESUMO
Extensive length polymorphism and heteroplasmy (multiple forms within an individual) of the D-loop region are observed in mitochondrial DNA of the white sturgeon (Acipenser transmontanus). The nucleotide sequence of this region, for both a short and a long form, shows that the differences are due to variable numbers of a perfect 82-bp direct repeat. We propose a model for the replicative origin of length differences, involving a competitive equilibrium between the heavy strand and the D-loop strand. This model suggests that frequent misalignment in the repeat region prior to elongation, facilitated by a stable secondary structure in the displaced strand, can explain both the polymorphism and heteroplasmy in this species.
Assuntos
Replicação do DNA , DNA Mitocondrial/genética , Peixes/genética , Modelos Genéticos , Polimorfismo de Fragmento de Restrição , Animais , Sequência de Bases , DNA Mitocondrial/metabolismo , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Sequências Repetitivas de Ácido NucleicoAssuntos
Apoproteínas/genética , Grupo dos Citocromos b/genética , DNA Mitocondrial/isolamento & purificação , Genes , Sequência de Aminoácidos , Animais , Apoproteínas/isolamento & purificação , Sequência de Bases , Grupo dos Citocromos b/isolamento & purificação , Citocromos b , Peixes , Dados de Sequência MolecularRESUMO
DNA probes derived from rat and human proenkephalin and prodynorphin genes have been used to localize these two opiate neuropeptide genes on human chromosomes. Hybridization of probes to Southern blots made with DNAs from a rodent-human somatic-cell hybrid panel indicates localization of proenkephalin to human chromosome 8 and of prodynorphin to human chromosome 20. In situ hybridization to metaphase chromosomes confirms these assignments and indicates regional localizations of proenkephalin to 8q23-q24 and of prodynorphin to 20p12-pter. A human genomic prodynorphin clone reveals a frequent two-allele TaqI polymorphism.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 20 , Cromossomos Humanos Par 8 , Encefalinas/genética , Precursores de Proteínas/genética , Alelos , Animais , Cricetinae , Marcadores Genéticos , Humanos , Células Híbridas , Camundongos , Hibridização de Ácido Nucleico , Polimorfismo de Fragmento de RestriçãoRESUMO
When used to probe Southern blots of TaqI-digested DNAs from unrelated individuals, p1-79, a 900 bp subclone of a random human cosmid, revealed at least 50 fragments, many of which were polymorphic. Each of 27 unrelated individuals tested with p1-79 displayed a distinct band pattern. Similar variation was seen with several other enzymes, including HaeIII, MspI, PstI and PvuII, whereas other enzymes yielded primarily large fragments of greater than 40 kb. In situ hybridization of p1-79 showed that the loci of hybridization are clustered on human chromosome band 1p36; localization of all TaqI fragments to chromosome 1 was confirmed with a human-rodent somatic cell hybrid panel. DNA sequencing of p1-79 revealed several copies of a 39 bp repeat whose variation in copy number might be the basis of the observed length polymorphisms. Studies of 3-generation Utah families suggest that the numerous restriction fragments homologous to p1-79 are inherited as haplotypes, implying that recombination within this cluster of loci is rare and allowing the cluster to serve as a useful marker for human gene mapping.
Assuntos
Cromossomos Humanos Par 1 , Desoxirribonucleases de Sítio Específico do Tipo II , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Sequências Repetitivas de Ácido Nucleico , Animais , Bandeamento Cromossômico , Mapeamento Cromossômico , Cricetinae , DNA/genética , Enzimas de Restrição do DNA , Marcadores Genéticos , Humanos , Células Híbridas , CariotipagemRESUMO
The polymorphic locus D19S11 consists of four closely linked RFLPs: alpha, beta, delta, and gamma on chromosome 19p13.2----19cen, revealed by subclones p13-1-82 and p13-2-21 from cosmid 1-13. Here, we report that p13-1-25, an additional subclone of c1-13, reveals three insertion/deletion RFLPs, alpha, epsilon, and phi, at the D19S11 locus. In situ hybridization of p13-1-25 to metaphase chromosomes from a carrier of a 19/X translocation with a breakpoint near the centromere confirms localization of D19S11 to 19p. Studies with hydatidiform moles have generated assignments of specific restriction fragments to these three loci, and genotypic studies in three-generation families have indicated that they are closely linked. Loci alpha (also detected by p13-1-82) and phi each have but two common alleles, whereas epsilon has at least 33 alleles, including a null allele. Fifty unrelated individuals tested displayed unique fragment patterns on Taq I blots probed with p13-1-25. Applications of this probe include monitoring loss of chromosome 19 during tumorigenesis, monitoring engraftment of donor bone marrow after transplantation, testing for paternity, and mapping disease genes on chromosome 19.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 19 , Ligação Genética , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , DNA/genética , Feminino , Marcadores Genéticos , Humanos , Cariotipagem , Masculino , Linhagem , Translocação GenéticaRESUMO
Human gene mapping would be greatly facilitated if marker loci with sufficient polymorphism information content were generally available. As a source of such markers, we have used cosmids from a human genomic library. We have used a rapid method for screening random cosmids to identify those homologous to genomic regions especially rich in restriction fragment length polymorphisms (Litt and White 1985). This method allows whole cosmids to be used as probes against Southern transfers of genomic DNA; regions of cosmid probes homologous to repeated genomic sequences are rendered unable to anneal with Southern transfers by prehybridization of the probes with a vast excess of non-radioactive genomic DNA. From one cosmid (C1-11) identified by this procedure, we have isolated four single-copy probes, each of which identifies a polymorphic locus. Despite the existence of some linkage disequilibrium in this system, the polymorphism information content was computed as 0.73. Using a somatic cell hybrid mapping panel, we have mapped probes from cosmid 1-11 to human chromosome 12q. Additionally, in situ hybridization of the whole cosmid to metaphase spreads allowed more precise assignment of the locus to the region 12cen----q13. The locus revealed by probes from cosmid 1-11 has been designated D12S6.
