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R E Ferrell

Publications and source records attributed to R E Ferrell.

At least 199 records · Page 11Linked to original sources
PubMed1992

Comparison of five tandem repeat loci between humans and chimpanzees.

Five tandem repeat loci were studied in humans and chimpanzees using VNTR probes derived from human DNA. Shared alleles were found at three loci and were often the modal allele in one species but never in both. There was no difference in the mean number of alleles per locus. However, these species exhibited substantially different levels of gene diversity, with chimpanzees monomorphic at two loci. Evidence of reduced variability in chimpanzees corroborates earlier comparisons using isozymes and plasma proteins. Molecular mechanisms, population dynamics, or both may be responsible for these differences. Equal numbers of alleles per locus may reflect high mutation rates. By one test, chimpanzees were out of equilibrium at one locus, which may reflect a typing error or population substructure. The long divergence time, and the high probability of backward mutations, precludes accurate estimation of genetic distance between these species.

Alleles↗
PubMed1992

The gender-specific apolipoprotein E genotype influence on the distribution of plasma lipids and apolipoproteins in the population of Rochester, Minnesota. II. Regression relationships with concomitants.

The influence of the apolipoprotein E (Apo E) polymorphism and gender on the regression relationships between each of nine plasma lipid and apolipoprotein traits (total cholesterol; ln triglycerides; high-density-lipoprotein cholesterol; apolipoproteins AI, AII, B, and CII; ln CIII; and ln E) and four concomitants (age, weight, waist-to-hip ratio, and smoking) was studied in 507 unrelated individuals representative of the adult population of Rochester, MN. Analyses are presented separately for females and males. Each lipid and apolipoprotein trait exhibited at least one Apo E genotype-specific regression relationship with the concomitants investigated in this study. In most cases the heterogeneity of regression was associated with differences between the epsilon 32 and epsilon 33 genotype. This study documents that the influence of Apo E genotype on average levels of plasma lipids and apolipoproteins varies among subdivisions of the population defined by age, body size, and smoking status.

Adult↗
PubMed1992

Characteristics of polymorphism at a VNTR locus 3' to the apolipoprotein B gene in five human populations.

We have analyzed the allele frequency distribution at the hypervariable locus 3' to the apolipoprotein B gene (ApoB 3' VNTR) in five well-defined human populations (Kacharis of northeast India, New Guinea Highlanders of Papua New Guinea, Dogrib Indians of Canada, Pehuenche Indians of Chile, and a relatively homogeneous Caucasian population of northern German extraction) by using the PCR technique. A total of 12 segregating alleles were detected in the pooled sample of 319 individuals. A fairly consistent bimodal pattern of allele frequency distribution, apparent in most of these geographically and genetically diverse populations, suggests that the ApoB 3' VNTR polymorphism predates the geographic dispersal of ancestral human populations. In spite of the observed high degree of polymorphism at this locus (expected heterozygosity levels 55%-78%), the genotype distributions in all populations (irrespective of their tribal or cosmopolitan nature) conform to their respective Hardy-Weinberg predictions. Furthermore, analysis of the congruence between expected heterozygosity and the observed number of alleles reveals that, in general, the allele frequency distributions at this locus are in agreement with the predictions of the classical mutation-drift models. The data also show that alleles that are shared by all populations have the highest average frequency within populations. These findings demonstrate the potential utility of highly informative hypervariable loci such as the ApoB 3' VNTR locus in population genetic research, as well as in forensic medicine and determination of biological relatedness of individuals.

Alleles↗
PubMed1992

Apolipoprotein A-IV genetic polymorphism and its impact on quantitative traits in normoglycemic and non-insulin-dependent diabetic Hispanics from the San Luis Valley, Colorado.

Apolipoprotein A-IV exhibits a common two-allele polymorphism in several human populations studied to date. Using isoelectric focusing and immunoblotting, we have analyzed plasmas from 188 non-insulin-dependent diabetic and 238 normoglycemic Hispanic individuals from the San Luis Valley, Colorado, to determine APOA4 genotype frequencies and to estimate the impact of the genotypes on quantitative traits. The frequencies of the two common alleles, APOA4*1 and APOA4*2, were 0.929 and 0.069, respectively, in normal subjects and 0.901 and 0.096, respectively, in diabetics. The third rare allele, APOA4*3, was detected sporadically in both groups. We studied the impact of APOA4 polymorphism on the levels of total plasma cholesterol, HDL cholesterol and its subfractions (HDL3 and HDL2), LDL cholesterol, triglycerides, glucose, and insulin. We observed no significant effect of the APOA4 polymorphism on any trait in diabetics. However, we did note a significant sex-specific effect in normoglycemic females on the level of total HDL cholesterol (p = 0.001) and its subfractions HDL2 (p = 0.043) and HDL3 (p = 0.001). The effect of the APOA4*2 allele in normal Hispanic females was to lower the total HDL, HDL2, and HDL3 cholesterol by 8.75 mg/dl, 2.37 mg/dl, and 5.36 mg/dl, respectively, compared to the common APOA4*1 allele.

Adult↗
PubMed1992

Apolipoprotein H (beta-2-glycoprotein I) polymorphism in Asians.

Apolipoprotein H (APOH) (beta-2-glycoprotein I) polymorphism has been studied in 1159 Asians. The sample included 872 Chinese, 179 Asiatic Indians (Dravidian), 91 Filipinos, and 17 Malays. APOH polymorphism was determined by isoelectric focusing of sera in thin-layer polyacrylamide gels containing 3 M urea followed by immunoblotting. The frequencies of the three alleles--APOH*1, APOH*2, and APOH*3--were found to be 0.031, 0.900, and 0.069 in the Chinese; 0.061, 0.866, and 0.073 in the Dravidian Indians; 0.055, 0.923, and 0.022 in the Filipinos; and 0.088, 0.882, and 0.029 in the Malays. The phenotypic distribution was at Hardy-Weinberg equilibrium in all the populations.

Adult↗
PubMed1992

Caucasian genes in American blacks: new data.

Data on 15 polymorphic protein-coding loci are used to estimate the proportion of Caucasian genes in U.S. blacks from the greater-metropolitan area of Pittsburgh. Allele frequencies from U.S. whites of the same region and from a sample of Nigerians are used as representatives of the genetic contributions of the source populations between which admixture has occurred. These materials provide 18 unique variants that occur exclusively in the blacks and 5 variants that are restricted to the Caucasians only. As a result, when all segregating alleles (52) at these 15 loci are considered, the proportion (mean +/- SE) of Caucasian genes in U.S. blacks (25.2% +/- 2.7%) is estimated with a precision much better than that of all other previous estimates. The estimate based on the frequencies of these 18 unique variants of African origin (24.8% +/- 6.2%) is also consistent with the pooled estimate obtained from the 15 loci by the weighted least-square method. The homogeneity of locus-specific estimates of admixture indicates that these loci are appropriate for studying the proportion of black genes in any admixed population involving African admixture. The advantages of employing such loci for genetic-epidemiologic studies in U.S. blacks is discussed in the context of the availability of these large number of unique African variants at these protein loci.

Alleles↗
PubMed1991

A germ line mutation in exon 5 of the p53 gene in an extended cancer family.

Germ line p53 point mutations have been reported for some families with Li-Fraumeni syndrome, a syndrome characterized by a dominantly inherited increased susceptibility for the development of early age of onset neoplasms of diverse origin in multiple family members. All of the initially reported p53 germ line mutations have been found exclusively within a single conserved, nonpolymorphic region of the gene between condons 245 and 258. The restricted distribution of these inherited mutations has led to speculation that germ line p53 mutations have unique properties [B. Vogelstein, Nature (Lond.), 348: 681-682, 1990]. We report here on the identification of a p53 germ line mutation at codon 133 (ATG----ACG) in nine members of an extended Li-Fraumeni syndrome family. This mutation leads to an amino acid substitution in the protein and is shown to completely cosegregate with Li-Fraumeni syndrome associated cancer in this family. Its location extends the region of the p53 gene where inherited mutations predisposing to cancer are observed and suggests that their distribution may be diverse.

Adult↗
PubMed1991

Genetic studies of human apolipoproteins. XVII: Population genetics of apolipoprotein polymorphisms in American Samoa.

Variation in human apolipoprotein genes is a major source of phenotypic differences in human lipid metabolism. Data regarding genetic variation at apolipoprotein loci in various populations are only beginning to accumulate, and they suggest that different populations vary widely in distribution of apolipoprotein alleles. Using isoelectric focusing-immunoblotting techniques, we screened 67 serum samples from self-identified Samoan residents of American Samoa to investigate structural variation at six apolipoprotein loci: A-I, A-II, A-IV, C-II, E, and H. The APO A-I, A-II, and C-II loci were found to be monomorphic by isoelectrical focusing. In Samoans, the common three-allele polymorphism was observed for APO E, with no striking differences in frequencies from Caucasian populations. The three common alleles of the APO H locus also were identified; however, frequencies of the less common alleles (APO H*I and APO H*3) were different from those observed elsewhere for Caucasians.

Adult↗
PubMed1991

Apolipoprotein A-IV polymorphism, and its role in determining variation in lipoprotein-lipid, glucose and insulin levels in normal and non-insulin-dependent diabetic individuals.

Apolipoprotein A-IV (apo A-IV) is a major component of several lipoprotein particles and may, therefore, play an important role in lipid metabolism. Genetic polymorphism of apo A-IV has been reported in humans and several other animal species. The presence of two common alleles, apo A-IV * 1 and apo A-IV * 2 has been documented in several human populations. In this investigation, we have determined apo A-IV polymorphism by isoelectric focusing-immunoblotting in 82 non-insulin-dependent diabetic and 204 control non-Hispanic Whites from the San Luis Valley, Colorado. We have also estimated the impact of apo A-IV polymorphism on eight quantitative traits: total cholesterol, HDL-cholesterol, HDL3 and HDL2-cholesterol, LDL-cholesterol, triglycerides, fasting glucose and fasting insulin. No statistically significant difference was seen in apo A-IV allele frequencies between the control and diabetics, and these frequencies were comparable with those reported for U.S. White and European populations. Among controls, the impact of the apo A-IV polymorphism was significant on LDL-cholesterol (P = 0.04) in females and on fasting insulin levels (P = 0.06) in males. In diabetics, the effect was significant on insulin (P = 0.03) levels in males only. Furthermore, our data suggest that when making comparison of lipid profiles between the controls and diabetics the presence or absence of common apo A-IV phenotypes should be taken into account as these appear to effect these comparisons.

Adult↗
PubMed1991

A population genetic study of six VNTR loci in three ethnically defined populations.

To investigate the population genetic characteristics of VNTR polymorphisms in human populations, we have studied the allele frequency distribution of six VNTR loci (D1S57, RB1, D1S77, D1S61, alpha-globin 5'HVR, D1S76) in three well-defined populations (Kachari of Northeast India; Dogrib Indian of Canada; and New Guinea Highlander of Papua New Guinea). Even though the number of alleles sampled is limited, 48 to 92 alleles per locus per population, significant variation is noticed in the number of alleles per locus for all the populations. Using alternate summary measures, we have observed that genotype distributions at the six VNTR loci apparently conform to their respective Hardy-Weinberg predictions. Multilocus genotype profiles of the individuals in each of the three populations suggest that the VNTR alleles are independently segregating with the exception of the two linked loci D1S76 and D1S77. Lack of fit of all VNTR loci to one particular model of mutational change, either the Infinite Allele Model or the Stepwise Mutation Model, suggests more than one mechanism for production of new VNTR alleles. This study also indicates that increased heterozygosity at VNTR loci in comparison to protein and blood group loci may lead to more accurate estimates of genetic distance.

Alleles↗
PubMed1991

Ultrasound screening of first-degree relatives of patients with an abdominal aortic aneurysm.

The pedigrees were constructed of 43 patients (probands) who underwent resection of an abdominal aortic aneurysm. Seven probands (16.2%) had a first-degree relative (parent, sibling, child) known to have had an abdominal aortic aneurysm (multiplex family). To determine the prevalence of undiagnosed abdominal aortic aneurysm, ultrasound screening of first-degree relatives over age 40 years was undertaken. Of 202 eligible relatives, 103 (51.0%) were screened. An occult abdominal aortic aneurysm was defined as an infrarenal aortic diameter greater than 3.0 cm or an infrarenal/suprarenal aortic diameter ratio of greater than 1.5. An incipient abdominal aortic aneurysm was defined as a clear focal bulge of the infrarenal aorta, which was less than 3.0 cm in greatest diameter. Four of 103 relatives (3.9%) were found to have an occult abdominal aortic aneurysm (age/sex: 57M, 60M, 62F, 65M), and three (2.9%) were found with an incipient abdominal aortic aneurysm (age/sex: 56M, 60M, 67F). These smaller abdominal aortic aneurysms were in patients younger than the operated probands (average age men, 67 years; women, 69 years). Six of seven individuals were in families previously considered simplex, increasing the actual multiplex family frequency from 16.2% to 27.9%. All seven new abdominal aortic aneurysms were found in the 49 siblings age 55 years or older. There were no abdominal aortic aneurysms found in the 39 relatives under age 55 years, in 14 children ages 50 to 59 years or in one parent. Therefore of the siblings age 55 years or older, 5/20 men (25.0%) and 2/29 women (6.9%) were found to have a previously undiagnosed abdominal aortic aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1991

Abdominal aortic aneurysm: results of a family study.

Data pertaining to abdominal aortic aneurysm among first-degree relatives of 91 patients with abdominal aortic aneurysm are presented. The percentage of families with at least one affected first-degree relative of the proband (multiplex families) was 15.4%. In 21.4% of multiplex families parent-offspring transmission of abdominal aortic aneurysm was noted; in the remaining families only siblings were affected. The mean age at onset among probands was 67.3 years; that among all affected was 67.4 years. No statistically significant difference in the mean ages at onset between genders was noted. Among affected siblings of probands, the sex ratio, male:female, was 1.33:1, which is not significantly different from 1:1. The relative risk of developing an abdominal aortic aneurysm was 3.97 for fathers, 4.03 for mothers, 9.92 for brothers, and 22.93 for sisters.

Age Factors↗
PubMed1991

Genetic studies of human apolipoproteins. XVI. APOE polymorphism and cholesterol levels in the Mayans of the Yucatan Peninsula, Mexico.

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).

Alleles↗
PubMed1991

A simplified method for screening the apolipoprotein E polymorphism.

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.

Adult↗
PubMed1991

Population genetics of alpha-1-antitrypsin polymorphism in US whites, US blacks and African blacks.

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.

Africa↗
PubMed1991

Genetic polymorphisms in southwest Alaskan Eskimos.

Allele frequencies of 28 genetic loci were determined in subsets (n ranged from 52 to 698) of a sample of Yupik-speaking Eskimos from southwestern Alaska. Five loci were monomorphic (Kell Kp (b+), ADA1, AK1, HBA, and PGDA). At the other loci, the most frequent alleles were AB00 (0.580), Fya (0.960), Jkb (0.513), Ms (0.333), CDe (0.591), ACPA (0.566), ESD1 (0.890), GLO2 (0.736), GPT1 (0.653), Hp2 (0.654), PGM1 (0.836), PGP1 (0.972), and UMPK1 (0.873). The most frequent immunoglobulin allotype Gm(1;21) occurred with a frequency of 0.829. The HLA alleles that occurred with highest frequencies were A24 (0.626), Bw48 (0.184), Cw3 (0.404), and DR4 (0.329). The average heterozygosity at all loci was 0.423. Based on the presence of the European allotype, Gm3;23;5,11,13, the proportion of European admixture in the Eskimo population was estimated to be 2.1%.

Alaska↗