RESUMO
OBJECTIVE: To map and identify susceptibility genes for NIDDM and for the intermediate quantitative traits associated with NIDDM. RESEARCH DESIGN AND METHODS: We describe the methodology and sample of the Finland-United States Investigation of NIDDM Genetics (FUSION) study. The whole genome search approach is being applied in studies of several different ethnic groups to locate susceptibility genes for NIDDM. Detailed description of the study materials and designs of such studies are important, particularly when comparing the findings in these studies and when combining different data sets. RESULTS: Using a careful selection strategy, we have ascertained 495 families with confirmed NIDDM in at least two siblings and no history of IDDM among the first-degree relatives. These families were chosen from more than 22,000 NIDDM patients, representative of patients with NIDDM in the Finnish population. In a subset of families, a spouse and offspring were sampled, and they participated in a frequently sampled intravenous glucose tolerance test (FSIGT) analyzed with the Minimal Model. An FSIGT was completed successfully for at least two nondiabetic offspring in 156 families with a confirmed nondiabetic spouse and no history of IDDM in first-degree relatives. CONCLUSIONS: Our work demonstrates the feasibility of collecting a large number of affected sib-pair families with NIDDM to provide data that will enable a whole genome search approach, including linkage analysis.
Assuntos
Diabetes Mellitus Tipo 2/genética , Característica Quantitativa Herdável , Idade de Início , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Finlândia , Predisposição Genética para Doença , Genótipo , Humanos , Insulina/sangue , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Fenótipo , Caracteres Sexuais , Estados UnidosRESUMO
The transgene-induced mutation 9257 and the spontaneous mutation twirler cause craniofacial and inner ear malformations and are located on mouse chromosome 18 near the ataxia locus ax. To map the human homolog of 9257, a probe from the transgene insertion site was used to screen a human genomic library. Analysis of a cross-hybridizing human clone identified a 3-kb conserved sequence block that does not appear to contain protein coding sequence. Analysis of somatic cell hybrid panels assigned the human locus to 18q11. The polymorphic microsatellite markers D18S1001 and D18S1002 were isolated from the human locus and mapped by linkage analysis using the CEPH pedigrees. The 9257 locus maps close to the centromeres of human chromosome 18q and mouse chromosome 18 at the proximal end of a conserved linkage group. To evaluate the role of this locus in human craniofacial disorders, linkage to D18S1002 was tested in 11 families with autosomal dominant nonsyndromic cleft lip and palate and 3 families with autosomal dominant cleft palate only. Obligatory recombinants were observed in 8 of the families, and negative lod scores from the other families indicated that these disorders are not linked to the chromosome 18 loci.
Assuntos
Evolução Biológica , Cromossomos Humanos Par 18 , Fenda Labial/genética , Fissura Palatina/genética , Face/anormalidades , Crânio/anormalidades , Alelos , Animais , Sequência de Bases , Mapeamento Cromossômico , Sequência Conservada , Primers do DNA , DNA Satélite , Frequência do Gene , Biblioteca Gênica , Ligação Genética , Marcadores Genéticos , Humanos , Células Híbridas , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da PolimeraseRESUMO
Ultrashort electromagnetic pulses are being increasingly produced by modern high power microwave and laser devices. These ultrashort pulses can produce electromagnetic transients in tissue that prompt safety questions concerning the possible exposure of living beings to ultrashort electromagnetic pulses. The existence of electromagnetic transients may permit meaningful advances in medical therapy and imaging. Electromagnetic transients, potential medical applications, and anticipated research avenues relevant to occupational health and safety issues are discussed.
Assuntos
Fenômenos Eletromagnéticos , Fenômenos Biofísicos , Biofísica , Humanos , Hipertermia Induzida , Membranas/efeitos da radiação , Micro-Ondas , Conformação Molecular/efeitos da radiação , Lesões por Radiação/etiologia , RadiografiaRESUMO
We have identified a polymorphic compound dinucleotide repeat sequence in intron 1 of the beta-amyloid precursor protein (APP) gene on chromosome 21. Using polymerase chain reaction (PCR) amplification of the locus, designated APPivs1, we detected 13 alleles in the CEPH family members (heterozygosity = 0.69). Lod score analysis showed complete linkage of the marker to the loci D21S210 and D21221.
Assuntos
Precursor de Proteína beta-Amiloide/genética , DNA , Marcadores Genéticos , Sequências Repetitivas de Ácido Nucleico , Alelos , Sequência de Bases , Cromossomos Humanos Par 21 , Primers do DNA/química , Eletroforese em Gel de Poliacrilamida , Humanos , Íntrons , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo GenéticoAssuntos
Cromossomos Humanos Par 13 , Proteínas de Ligação a DNA/genética , Polimorfismo Genético , Sequências Repetitivas de Ácido Nucleico , Sequência de Bases , Mapeamento Cromossômico , Primers do DNA , Reparo do DNA , Endonucleases , Humanos , Dados de Sequência Molecular , Proteínas Nucleares , Oligodesoxirribonucleotídeos , Reação em Cadeia da Polimerase , Fatores de Transcrição , Xeroderma Pigmentoso/genéticaRESUMO
A genetic linkage map of human chromosome 21q (HC21q) containing 43 markers genotyped by the polymerase chain reaction in the CEPH pedigrees is presented. The markers placed on this map are highly polymorphic with an average heterozygosity of 61%. The average interval size of the markers localized at 1000:1 odds is 2.5 cM. The map has a total length of 65.5 cM, with male and female lengths of 47.7 and 83.3 cM, respectively. The genotypes used in the construction of this map were subjected to rigorous error checking, which is reflected in the shorter map length compared to previous maps; the estimated error rate in genotyping is less than 0.04%. As noted in previous linkage maps there is increased recombination in females on proximal HC 21q and in the male in a region near the telomere. This map of HC 21 represents a highly informative and dense meiotic linkage map and will be useful in linking disease phenotypes to loci on this chromosome.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 21 , Feminino , Marcadores Genéticos , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo Genético , Sequências Repetitivas de Ácido Nucleico , Caracteres SexuaisRESUMO
We describe a highly polymorphic (GT)n repeat with 14 alleles that is closely linked to the amyloid precursor protein (APP) gene on human chromosome 21. This marker, D21S210, will be useful for studies of linkage of disorders such as Alzheimer disease to the APP gene.
Assuntos
Alelos , Precursor de Proteína beta-Amiloide/genética , Cromossomos Humanos Par 21 , Frequência do Gene , Ligação Genética/genética , Polimorfismo Genético/genética , Sequência de Bases , Feminino , Humanos , Masculino , Dados de Sequência Molecular , LinhagemRESUMO
To further develop the linkage map of human chromosome 21 (HC21), we have concentrated on identifying highly polymorphic markers based on dinucleotide repeat sequences such as (GT)n, as these are often highly polymorphic, are widespread throughout the human genome, and can be rapidly analyzed by the polymerase chain reaction. We report here nine (GT)n polymorphic markers from HC21.
Assuntos
Cromossomos Humanos Par 21 , Polimorfismo Genético , Sequências Repetitivas de Ácido Nucleico , Animais , Sequência de Bases , Mapeamento Cromossômico , DNA , Marcadores Genéticos , Humanos , Células Híbridas , Camundongos , Dados de Sequência MolecularRESUMO
We have detected a polymorphism in the 3' untranslated region of the AML1 gene, which is located at the breakpoint on chromosome 21 in the t(8;21)(q22;q22.3) translocation often associated with patients with acute myeloid leukemia. Informative CEPH families were genotyped for this polymorphism and used to localize the gene on the linkage map of human chromosome 21. The AML1 gene is located between the markers D21S216 and D21S211, in chromosomal band 21q22.3.
