Assuntos
Substituição de Aminoácidos , Anodontia/genética , Ectodisplasinas/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Incisivo/anormalidades , Sequência de Aminoácidos , Animais , Sequência de Bases , Ectodisplasinas/química , Genes Ligados ao Cromossomo X , Ácido Glutâmico/genética , Ácido Glutâmico/metabolismo , Glicina/genética , Glicina/metabolismo , Humanos , Incisivo/diagnóstico por imagem , Dados de Sequência Molecular , Mutação , Linhagem , Radiografia , Alinhamento de SequênciaRESUMO
Amelogenesis imperfecta (AI) is a collective term used to describe phenotypically diverse forms of defective tooth enamel development. AI has been reported to exhibit a variety of inheritance patterns, and several loci have been identified that are associated with AI. We have performed a genome-wide scan in a large Brazilian family segregating an autosomal dominant form of AI and mapped a novel locus to 8q24.3. A maximum multipoint LOD score of 7.5 was obtained at marker D8S2334 (146,101,309 bp). The disease locus lies in a 1.9 cM (2.1 Mb) region according to the Rutgers Combined Linkage-Physical map, between a VNTR marker (at 143,988,705 bp) and the telomere (146,274,826 bp). Ten candidate genes were identified based on gene ontology and microarray-facilitated gene selection using the expression of murine orthologues in dental tissue, and examined for the presence of a mutation. However, no causative mutation was identified.
Assuntos
Amelogênese Imperfeita/genética , Cromossomos Humanos Par 8 , Predisposição Genética para Doença , Amelogênese Imperfeita/patologia , Animais , Brasil , Mapeamento Cromossômico , Saúde da Família , Feminino , Perfilação da Expressão Gênica , Genes Dominantes , Genótipo , Humanos , Escore Lod , Masculino , Camundongos , Dente Molar/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , LinhagemRESUMO
Ongoing modernization in India has elevated the prevalence of many complex genetic diseases associated with a western lifestyle and diet to near-epidemic proportions. However, although India comprises more than one sixth of the world's human population, it has largely been omitted from genomic surveys that provide the backdrop for association studies of genetic disease. Here, by genotyping India-born individuals sampled in the United States, we carry out an extensive study of Indian genetic variation. We analyze 1,200 genome-wide polymorphisms in 432 individuals from 15 Indian populations. We find that populations from India, and populations from South Asia more generally, constitute one of the major human subgroups with increased similarity of genetic ancestry. However, only a relatively small amount of genetic differentiation exists among the Indian populations. Although caution is warranted due to the fact that United States-sampled Indian populations do not represent a random sample from India, these results suggest that the frequencies of many genetic variants are distinctive in India compared to other parts of the world and that the effects of population heterogeneity on the production of false positives in association studies may be smaller in Indians (and particularly in Indian-Americans) than might be expected for such a geographically and linguistically diverse subset of the human population.
Assuntos
Alelos , Frequência do Gene , Variação Genética , Idioma , Análise por Conglomerados , Elementos de DNA Transponíveis/genética , Europa (Continente) , Ásia Oriental , Deleção de Genes , Humanos , Índia/etnologia , Repetições de Microssatélites/genética , Oriente Médio , Polimorfismo Genético , SoftwareRESUMO
Seckel syndrome (SCKL) is a rare disease with wide phenotypic heterogeneity. A locus (SCKL1) has been identified at 3q and another (SCKL2) at 18p, both in single kindreds afflicted with the syndrome. We report here a novel locus (SCKL3) at 14q by linkage analysis in 13 Turkish families. In total, 18 affected and 10 unaffected sibs were included in the study. Of the 10 informative families, nine with parental consanguinity and one reportedly nonconsanguineous but with two affected sibs, five were indicative of linkage to the novel locus. One of those families also linked to the SCKL1 locus. A consanguineous family with one affected sib was indicative of linkage to SCKL2. The novel gene locus SCKL3 is 1.18 cM and harbors ménage a trois 1, a gene with a role in DNA repair.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 14 , Heterogeneidade Genética , Ligação Genética , Anormalidades Múltiplas/patologia , Adolescente , Adulto , Criança , Mapeamento Cromossômico , Consanguinidade , Feminino , Marcadores Genéticos , Transtornos do Crescimento/genética , Transtornos do Crescimento/patologia , Haplótipos , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Masculino , Microcefalia/genética , Microcefalia/patologia , Repetições de Microssatélites , Fenótipo , SíndromeRESUMO
We analyzed the CFTR locus in 83 Turkish cystic fibrosis patients to identify mutations, haplotypes, and the carrier frequency in the population. We detected 36 different mutations in 125 (75%) of the total 166 CF chromosomes. Seven novel mutations were identified: four missense (K68E, Q493P, E608G, and V1147I), two splice-site (406 -3T > C and 3849 +5G > A), and one deletion (CFTRdele17b,18). The data showed that the Turkish population has the highest genetic heterogeneity at the CFTR locus reported so far. The results of this thorough molecular analysis at the CFTR locus of a population not of European descent shows that CF is not uncommon in all such populations. The large number of mutations present, as well as the high heterogeneity in haplotypes associated with the mutations suggests that most of the mutations have persisted for a long time in the population. Consistently, the carrier frequency is assessed to be high, indicating that the disease in the population is ancient.