RESUMO
BACKGROUND/AIMS:The Tobago Afro-Caribbean population is a valuable resource for studying the genetics of diseases that show significant differences in prevalence between populations of African descent and populations of other ancestries. Empirical confirmation of low European and Native American admixture may help in clarifying the ethnic variation in risk for such diseases. We hypothesize that the degree of European and Native American admixture in the Tobago population is low.METHODS:Admixture was estimated in a random sample of 220 men, from a population-based prostate cancer screening survey of 3,082 Tobago males, aged 40 to 79 years. We used a set of six autosomal markers with large allele frequency differences between the major ethnic populations involved in the admixture process, Europeans, Native Americans and West Africans.RESULTS:The ancestral proportions of Tobago population are estimated as 94.0+/-1.2% African, 4.6+/-3.4% European and 1.4+/-3.6% Native American.CONCLUSIONS:We conclude that Tobago Afro-Caribbean men are predominantly of West African ancestry, with minimal European and Native American admixture. The Tobago population, thus, may carry a higher burden of high-risk alleles of African origin for certain diseases than the more admixed African-American population. Conversely, this population may benefit from a higher prevalence of protective alleles of African origin.
Assuntos
Masculino , Pneumonia Bacteriana , Escarro , População , População Negra , Região do Caribe , Trinidad e TobagoRESUMO
Elevated levels of lipoprotein(a) [Lp(a)] are associated with increased risk for coronary heart disease (CHD). However, racial differences in both Lp(a) levels and their associated CHD risk are observed, with African Americans having, on average, higher Lp(a) levels than US whites but not the expected increase in CHD risk. We determined Lp(a) levels and their correlates in a large cohort (n = 2379) of black and white girls, ages 9 to 10 years, at the baseline visit of a longitudinal study of obesity development, the National Heart, Lung, and Blood Institute Growth and Health Study. Lp(a) levels were available for 1269 girls. The median Lp(a) level in black girls was over 3-fold higher than that in white girls. Associations were examined between Lp(a) levels and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, adiposity, pubertal maturation stage, body fat patterning (triceps/truncal skinfold ratio), and dietary fat (Keys' score). In black girls multiple regression analysis identified LDL-C (P <.001) and adiposity (P =. 08) as predictors of Lp(a) levels. In white girls only LDL-C (P =. 02) was associated with Lp(a). In conclusion, the level of Lp(a) was significantly higher in black girls. Our study also revealed a racial difference in correlates of Lp(a), such as LDL-C and adiposity. Whether this racial difference is due to an underlying biologic difference or is merely a reflection of a greater statistical power to detect a relationship with the level, which was 2.5-fold higher in black girls than in white girls, needs further investigation.
Assuntos
População Negra , Lipoproteína(a)/sangue , População Branca , Análise de Variância , Antropometria , Criança , Comportamento Alimentar , Feminino , Humanos , Estudos Longitudinais , Análise de Regressão , Maturidade Sexual , Estatísticas não Paramétricas , Estados UnidosRESUMO
We analyzed the European genetic contribution to 10 populations of African descent in the United States (Maywood, Illinois; Detroit; New York; Philadelphia; Pittsburgh; Baltimore; Charleston, South Carolina; New Orleans; and Houston) and in Jamaica, using nine autosomal DNA markers. These markers either are population-specific or show frequency differences >45% between the parental populations and are thus especially informative for admixture. European genetic ancestry ranged from 6.8% (Jamaica) to 22.5% (New Orleans). The unique utility of these markers is reflected in the low variance associated with these admixture estimates (SEM 1.3%-2.7%). We also estimated the male and female European contribution to African Americans, on the basis of informative mtDNA (haplogroups H and L) and Y Alu polymorphic markers. Results indicate a sex-biased gene flow from Europeans, the male contribution being substantially greater than the female contribution. mtDNA haplogroups analysis shows no evidence of a significant maternal Amerindian contribution to any of the 10 populations. We detected significant nonrandom association between two markers located 22 cM apart (FY-null and AT3), most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations. The strength of this association and the substantial genetic distance between FY and AT3 emphasize the importance of admixed populations as a useful resource for mapping traits with different prevalence in two parental populations.
Assuntos
Alelos , População Negra/genética , Genética Populacional , África/etnologia , Negro ou Afro-Americano , Elementos Alu/genética , População Negra/classificação , DNA Mitocondrial/genética , Europa (Continente)/etnologia , Feminino , Frequência do Gene , Pool Gênico , Marcadores Genéticos , Haplótipos/genética , Humanos , Jamaica , Desequilíbrio de Ligação , Masculino , Polimorfismo Genético , Razão de Masculinidade , Estados Unidos , Cromossomo Y/genéticaRESUMO
We analyzed the European genetic contribution to 10 populations of Africans descent in the United States (Maywood, Illinois; Detroit; New York; Philadelphia; Pittsburgh; Baltimore; Charleston, South Carolina; New Orleans; and Houston) and in Jamaica, using nine autosomal DNA markers. These markers either are population-specific or show frequency differences >45 percent between the parental populations and are thus especially informative for admixture. European genetic ancestry ranged from 6.8 percent (Jamaica) to 22.5 percent (New Orleans). The unique utility of these markers is reflected in the low variance associated with these admixture estimates (SEM 1.3 percent -2.7 percent). We also estimated the male and female European contribution to African Americans. on the basis of informative mtDNA (haplogroups H and L) and Y Alu polymorphic markers. Results indicate a sex-biased gene flow from Europeans, the male contribution being substantially greater that the female contribution. mtDNA haplogroups analysis shows no evidence of a significant maternal Amerindian contribution to any of the 10 populations. We detected significant nonrandom association between two markers located 22 cM apart (FY-null and AT3), most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations. The strength of this association and the substantial genetic distance between FY and AT3 emphasize the importance of admixed populations as a useful resources for mapping traits with different prevalence in two parental populations (AU)
Assuntos
Feminino , Humanos , Masculino , Alelos , Genética Populacional , /genética , África/etnologia , Elementos Alu/genética , Negro ou Afro-Americano , DNA Mitocondrial/genética , Europa (Continente)/etnologia , Frequência do Gene , Pool Gênico , Marcadores Genéticos , Haplótipos/genética , Jamaica , Desequilíbrio de Ligação , /classificação , Polimorfismo Genético , Razão de Masculinidade , Estados Unidos , Cromossomo Y/genéticaRESUMO
Native Americans have been classified into four founding haplogroups with as many as seven founding lineages based on mtDNA RFLPs and DNA sequence data. mtDNA analysis was completed for 83 Yanomami from eight villages in the Surucucu and Catrimani Plateau regions of Roraima in northwestern Brazil. Samples were typed for 15 polymorphic mtDNA sites (14 RFLP sites and 1 deletion site), and a subset was sequenced for both hypervariable regions of the mitochondrial D-loop. Substantial mitochondrial diversity was detected among the Yanomami, five of seven accepted founding haplotypes and three others were observed. Of the 83 samples, 4 (4.8%) were lineage B1, 1 (1.2%) was lineage B2, 31 (37.4%) were lineage C1, 29 (34.9%) were lineage C2, 2 (2.4%) were lineage D1, 6 (7.2%) were lineage D2, 7 (8.4%) were a haplotype we designated "X6," and 3 (3.6%) were a haplotype we designated "X7." Sequence analysis found 43 haplotypes in 50 samples. B2, X6, and X7 are previously unrecognized mitochondrial founding lineage types of Native Americans. The widespread distribution of these haplotypes in the New World and Asia provides support for declaring these lineages to be New World founding types.
Assuntos
DNA Mitocondrial , Evolução Molecular , Variação Genética , Indígenas Sul-Americanos/genética , Adulto , Brasil , DNA Mitocondrial/genética , DNA Mitocondrial/história , Emigração e Imigração/história , Feminino , Efeito Fundador , Haplótipos , História Antiga , Humanos , Indígenas Sul-Americanos/história , Masculino , Polimorfismo de Fragmento de RestriçãoRESUMO
X-linked progressive cone dystrophy (COD1) causes progressive deterioration of visual acuity, deepening of central scotomas, macular changes, and bull's-eye lesions. The cone electroretinography (ERG) is variably abnormal in affected males, and the rod ERG may also be abnormal. The clinical picture of heterozygous females ranges from asymptomatic to a widespread spectrum of cone-mediated dysfunction. A prior linkage study demonstrated linkage between the COD1 locus and the marker locus DXS84, assigned to Xp21.1, with no recombination. In the present study, we have clinically characterized a large four-generation family with COD1 and have performed a linkage analysis using seven polymorphic markers on the short arm of the X chromosome. No recombination was observed between the disease and the marker loci DXS7 and MAOA, suggesting that the location of COD1 is in the region Xp11.3, distal to DXS84 and proximal to ARAF1.
Assuntos
Ligação Genética , Células Fotorreceptoras Retinianas Cones/patologia , Retinose Pigmentar/genética , Cromossomo X/genética , Criança , Mapeamento Cromossômico , Feminino , Fundo de Olho , Marcadores Genéticos , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo Genético/genética , Polimorfismo de Fragmento de Restrição , Recombinação Genética , Retinose Pigmentar/patologia , Caracteres SexuaisRESUMO
Apolipoprotein A-IV (apoA-IV, protein; APOA4, gene) is a major constituent of high-density lipoprotein (HDL) and triglyceride-rich lipoprotein particles, but its precise function in lipid metabolism is still uncertain. We have determined APOA4 genetic polymorphism in 285 randomly selected Melanesians from the Solomon Islands and have evaluated its significance in lipid metabolism. By using isoelectric focusing and immunoblotting techniques, a variant pattern, indistinguishable from the APOA4*2 allele uniquely found in white populations at a frequency of about 8%, was detected at a relatively high frequency (19%) in the Melanesian sample. Polymerase chain reaction (PCR) amplification and DNA sequencing of the 3' end of the APOA4 gene revealed that the Melanesian mutation is distinct from the known APOA4*2 mutation and that it involves a four-amino acid deletion in the evolutionarily conserved carboxyl-terminal region in the apoA-IV protein, which consists of four repeats of four amino acids each. After adjustment for concomitant variables, we investigated the impact of the deletion polymorphism on plasma levels of cholesterol, triglycerides, apoA-I, apoA-II, and apoE. A significant (P = .02) and gene-dosage effect was observed on the plasma levels of apoA-I and apoA-II: these levels were lowest in individuals homozygous for the deletion allele (D), intermediate in heterozygotes (ND), and highest in homozygous individuals for the normal allele (N). The average effect of the APOA4*D allele was to lower apoA-I and apoA-II by 8 mg/dL and 2 mg/dL, respectively, and the APOA4 polymorphism accounted for about 3% of the phenotypic variance in both cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Apolipoproteínas A/genética , Deleção de Genes , Metabolismo dos Lipídeos , Polimorfismo Genético , Alelos , Sequência de Bases , Genótipo , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , FenótipoRESUMO
The apolipoprotein (apo) E polymorphism has been related to differences in lipoprotein metabolism and lipid/lipoprotein concentrations in a number of studies. Whether these associations are seen in insulin-dependent diabetes mellitus (IDDM), which itself affects many of the same aspects of lipoprotein metabolism as does the apo E polymorphism, is unknown. The present study is an investigation into the influence of apo E phenotype on lipoprotein concentrations in a large group of IDDM patients (n = 433) participating in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. The frequency of the three apo E alleles 2, 3, and 4 did not differ in this population from that reported in general white populations. Although the diabetic subjects show the same trends as seen in the general population, ie, apo E-2 is associated with lower and apo E-4 with higher low-density lipoprotein cholesterol (LDLc) compared with apo E3 (P less than .03), they also show relationships with glycemic control that influence the relative levels of lipid measures with respect to apo E phenotype. Results also raise the possibility that lipoprotein composition varies according to apo E phenotype in IDDM.
Assuntos
Apolipoproteínas E/genética , Diabetes Mellitus Tipo 1/sangue , Lipoproteínas/sangue , Adulto , Alelos , Apolipoproteínas E/sangue , Diabetes Mellitus Tipo 1/genética , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Caracteres SexuaisRESUMO
A simple method for screening populations for the apolipoprotein E polymorphism which involves isoelectric focusing of delipidated samples on polyacrylamide gels of pH 4.5-5.8 followed by immunoblotting using a double-antibody technique is presented. The method is a synthesis of two previously published procedures and works well on samples that have been stored for as long as 15 years.
Assuntos
Apolipoproteínas E/genética , Testes Genéticos , Polimorfismo Genético , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , Feminino , Humanos , Focalização Isoelétrica , Estudos Longitudinais , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The purpose of this work was to examine the influence of apolipoprotein gene variation on plasma lipid levels in a population of Mayan Indians of the Yucatán Peninsula, Mexico. Four restriction enzymes: XmnI, PstI, SstI, and PvuII, were used to detect restriction fragment length polymorphisms (RFLP) within the region of the apolipoprotein AI/CIII/AIV gene cluster. The frequencies of these polymorphisms in this Mayan population were similar to those reported for other Amerindian populations, but differed widely from those reported for Caucasian populations. The XmnI and SstI RFLPs were informative for association studies in this population, and we analyzed their influence on the quantitative variation of plasma cholesterol and triglycerides. Using a nonparametric analysis of variance, it is shown that the presence of the XmnI restriction site had a significant effect in lowering plasma cholesterol, whereas the presence of the restriction site for SstI had a significant effect in raising plasma triglycerides. Consequently, genetic indicators of both low and high risk for lipid-related diseases, such as atherosclerosis and coronary heart disease, seem to be present within the same gene region in this Mayan population.
Assuntos
Apolipoproteína A-I/genética , Colesterol/sangue , DNA/genética , Indígenas Norte-Americanos/genética , Família Multigênica/genética , Polimorfismo Genético/genética , Triglicerídeos/sangue , Adulto , Feminino , Genótipo , Humanos , Masculino , México/etnologia , Pessoa de Meia-IdadeRESUMO
An isoelectric focusing (IEF) procedure in an ultra-narrow pH range, 4.2-4.9, has been utilized to detect alpha 1-antitrypsin or alpha 1-protease inhibitor (PI) allele products in 2 US white and 3 US black populations as well as 1 native African black population. In addition to the 3 common alleles PI*M1, PI*M2 and PI*M3, products of the 4th allele PI*M4 have been identified in US whites at low-level frequency. The presence of the PI*S, PI*Z and PI*I alleles has also been verified in our population samples. While the PI*S allele is present at a polymorphic level in US whites, it is only present sporadically in US blacks and is completely absent in African blacks. The PI*Z allele was not detected in the black populations tested. The PI allele frequency data have been used to calculate white admixture in US blacks.
Assuntos
População Negra/genética , Frequência do Gene/genética , Polimorfismo Genético/genética , População Branca/genética , alfa 1-Antitripsina/genética , África/etnologia , Mapeamento Cromossômico , Humanos , Estados Unidos/etnologiaRESUMO
Structural variation at the APOE locus is a major determinant of interindividual differences in cholesterol levels in populations at large. We have determined APOE structural polymorphism and estimated its impact on total cholesterol in the Mayans of the Yucatan Peninsula from Mexico. A unique pattern of APOE allele frequency distribution was observed, with no example of the APOE*2 allele and a relatively low incidence (9%) of the APOE*4 allele, giving rise to the lowest average heterozygosity at the APOE locus observed to date. The reported elevating affect of the APOE*4 allele on cholesterol has been found to be absent in the Mayans; several possible explanations which may account for the absence of this affect are discussed. In addition to APOE the gene products of five other apolipoprotein loci were screened and low frequency variation, possibly due to European admixture, was observed in two systems (APOH and APOA-IV).
Assuntos
Apolipoproteínas E/genética , Colesterol/sangue , Indígenas Norte-Americanos , Alelos , Análise de Variância , Apolipoproteína C-III , Apolipoproteína E2 , Apolipoproteína E3 , Apolipoproteína E4 , Apolipoproteínas A/genética , Apolipoproteínas C/genética , Criança , Colesterol/biossíntese , Frequência do Gene , Glicoproteínas/genética , Humanos , Immunoblotting , México , Polimorfismo Genético , beta 2-Glicoproteína IRESUMO
Genetically determined structural variation in the gene products of various apolipoproteins plays a significant role in modulating lipid levels in the population at large. However, due to tedious and cumbersome experimental problems involved, the detailed characterization of this genetic variation has been limited. The recent development of simple and sensitive isoelectric focusing and immunoblotting methods has circumvented these technically associated problems to a large extent, and this has allowed us to expand the genetic data on various apolipoproteins to previously uncharacterized populations. We have reviewed here these isoelectric focusing and immunoblotting methods. A comprehensive listing of allele frequencies has also been given for the polymorphic apolipoproteins.
Assuntos
Apolipoproteínas/genética , Immunoblotting/métodos , Frequência do Gene , Humanos , Polimorfismo GenéticoRESUMO
An improved method has been developed for the reliable classification of different C1R genetic variant forms from human serum or plasma. The method combines the use of neuraminidase-digested samples followed by monodimensional isoelectric focusing in the pH range 5 to 8 followed by immunoblotting. The method yields a simple pattern, with one major band in homozygote and two major bands in heterozygote cases.
Assuntos
Tipagem e Reações Cruzadas Sanguíneas/métodos , Complemento C1r/análise , Heterozigoto , Homozigoto , Humanos , Concentração de Íons de Hidrogênio , Immunoblotting , Focalização Isoelétrica , Neuraminidase/metabolismo , FenótipoRESUMO
Apolipoprotein C-III (APO C-III) is a structural component of very-low-density and high-density lipoprotein particles and is an inhibitor of lipoprotein lipase. In a study of genetic variation of apolipoproteins in the Mayan population of the Yucatán peninsula, we observed a quantitative polymorphism in APO C-III levels. This polymorphism is expressed as variation in immunoblot staining intensity following isoelectric focusing and as variation in plasma levels of APO C-III determined by radial immunodiffusion. This variation is consistent with the presence in Mayans of an allele associated with low levels of plasma APO C-III which we have designated APO C-III*D. Analysis of the distribution of APO C-III levels yields a gene frequency estimate for the deficiency allele of 0.59. There is a significant positive correlation between total plasma APO C-III levels and total plasma cholesterol and triglyceride levels, the lowest levels of cholesterol and triglycerides being seen in individuals homozygous for the deficiency allele. This observation is consistent with the proposed role of APO C-III in lipoprotein metabolism. Family data to determine whether this deficiency allele is due to mutation at the APO C-III structural locus were not available. However, molecular analysis using cloned probes from the APO A-I/C-III/A-IV gene cluster revealed no gross DNA rearrangement or deletion of sequences in this region in homozygous deficient individuals.
Assuntos
Apolipoproteínas C/genética , Indígenas Centro-Americanos/genética , Apolipoproteína C-III , Variação Genética , Humanos , Focalização Isoelétrica , Polimorfismo GenéticoRESUMO
The importance of surnames in genetic studies has been recognized for a century or so. While the ethnic affiliations of individuals are ordinarily established in genetic studies by admixture analysis based on gene frequencies, often there are implicit assumptions in these attempts that are difficult to validate in the absence of detailed ethnohistories. In northern Chile and western Bolivia, where genetic admixture has been known to occur among the Aymara Indians and Spanish Caucasoids, the naming pattern (parental patriand matrinyms) allowed us to classify individuals on the basis of the frequency of Aymara names into 9 'ethnic' groups. From a sample of 2525 individuals it is shown that admixture occurred in lineages nonrandomly, implying assortative mating of surnames. Admixture and genetic distance analysis on the basis of 31 genetic markers on approximately 1700 of these individuals reveals that there is a reasonable agreement of ethnic classification of individuals by name and phenotype data on genetic markers. The Aymara-named groups are shown to be predominantly Amerindian (89%) in their genetic profiles. Individuals whose current naming pattern is basically Spanish also exhibit a substantial fraction of genes of Amerindian origin (67%). Presence of some rare alleles not found in Amerindian or Spanish Caucasoids in the admixed groups suggest infiltration of Negroid genes in the past.
Assuntos
Etnicidade , Frequência do Gene , Nomes , Bolívia , Chile , Feminino , Marcadores Genéticos , Humanos , MasculinoRESUMO
Although subcomponents C1r and C1s of the first complement component, C1, have been established to be in the same linkage group as the proline-rich protein gene cluster on chromosome 12p13.2, no direct analysis of linkage between the C1R and C1S structural gene loci has been available. We have detected through a population screening study 5 families which are heterozygous at the structural loci for both C1R and C1S. Three of the 5 families, 21 individuals, were informative for linkage. A maximum lod score of 1.505 at theta = 0.00 was found in a two-point analysis between C1R and C1S. Ten populations were screened for structural variation at the C1S locus. Only US Whites and a Kodiak Island Eskimo group expressed heterogeneity. The frequencies of the designated alleles, C1S*1 and C1S*2, were 0.992 and 0.007, respectively, in the US White population and 0.998 and 0.002, respectively, in the Kodiak Island Eskimo population. In addition, the product of a putative new allele, designated C1S*4, was observed in a single US White individual but segregation of this variant was not observed in the limited family data available.
Assuntos
Proteínas Sanguíneas/genética , Enzimas Ativadoras do Complemento/genética , Complemento C1s/genética , Ligação Genética , Genética Populacional , Complemento C1/genética , Complemento C1r , Feminino , Frequência do Gene , Humanos , Masculino , Linhagem , Fenótipo , Grupos Raciais , Estados UnidosRESUMO
Thin-layer polyacrylamide gel isoelectric focusing over the pH range 3.5-5 followed by immunoblotting was used to investigate the occurrence and frequency of genetic variation in corticosteroid-binding globulin (CBG). Plasma samples from US Caucasians (n = 105) and US Blacks (n = 106) from Pittsburgh, Pa., Canadian Indians from Vancouver Island (n = 91) and Nigerian Blacks (n = 116) were analyzed. A complex isoprotein pattern was observed in all individuals tested. Reduction of this pattern to a single primary band following neuraminidase treatment indicates that the observed intraindividual variation is due to variation in the number of sialic acid residues associated with CBG. The CBG variant pattern consisted of a series of isoprotein bands having the same mobility as the common pattern, and a second series of bands at a more acidic isoelectric point. This pattern is consistent with heterozygosity for a rare CBG allele.
Assuntos
Proteínas Sanguíneas/genética , Transcortina/genética , Western Blotting , Variação Genética , Humanos , Focalização Isoelétrica , FenótipoRESUMO
An isoelectric focusing procedure in an ultranarrow pH range (5.0-5.5) polyacrylamide gel is described for the determination of superoxide dismutase (SOD) phenotypes. The occurrence of the rare SOD A*2 allele in the Caucasian population of Utah is also reported at a polymorphic frequency (0.011). The presence of the SOD A 2 unique allele in the Mormons of Utah is compatible with their historical affinity with Scandinavians.