bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locus and population specific evolution in HLA class II genes
Authors: VALDES A. M. , McWEENEY S. K. , MEYER D. , NELSON M. P. , THOMSON G. 
Published: March 2003

The population genetics of the HLA class II loci was studied with reference to variation in the frequency of (a) alleles at a locus and (b) amino acids at specific sites. Variation was surveyed at 4 loci (DRB1, DQA1, DQB1, and DPB1) in 22 populations from the Twelfth International Histocompatibility Workshop (Saint‐Malo, 1996). Allele and amino acid variation was measured by computing heterozygosity and the effective number of alleles. Substantial variations in polymorphism were observed among the various populations and loci studied. In the majority of the populations, DRB1 has the highest heterozygosity and effective number of alleles. As previously shown, the Amerindian populations have lower levels of allelic diversity when compared to other populations. At the amino acid level, DRB1 antigen recognition sites (ARS) have the highest heterozygosities and effective number of alleles. For the other loci (DPB1, DQA1, and DQB1) for which there is no crystal structure and for which ARS sites were inferred from DRB1, non‐ARS sites were often among the sites with highest levels of variation. It is possible that these putative non‐ARS sites do play a role in antigen presentation.The homozygosity test for neutrality was applied to allele and amino acid data. Of the four HLA class II loci studied, only DPB1 failed to show evidence of balancing selection. DQB1 and DQA1 depart significantly from neutrality in the largest number of populations. Genetic distances between populations were computed based on frequency of alleles and amino acids at ARS sites.
REPORT on the Sixth International Workshop on Chromosome 9 held at Denver, Colorado, U.S.A., 27 October 1998
Authors: CHADWICK B. P. , CAMPBELL L. J. , JACKSON C. L. , OZELIUS L. , SLAUGENHAUPT S. A. , STEPHENSON D. A. , EDWARDS J. H. , WIEST J. , POVEY S. 
Published: March 2003

A meeting on chromosome 9 was held on Tuesday, 27 October 1998 in Denver, with 38 participants (see appendix). Since the last meeting several of the positional cloning efforts on chromosome 9q have come to fruition, and the most detailed discussion was on 9p. Dr Ian Dunham from the Sanger Centre explained the strategy to be used for sequencing chromosome 9, and encouraged collaboration in the preparatory mapping. He indicated that some priority could be given to those regions where people in the field had a strong interest and could identify relevant PAC clones.At this short meeting it was clearly not possible to construct a comprehensive map of chromosome 9, and it was decided that efforts should be made to maintain links to sources of information on the chromosome 9 web page (http://www.gene.ucl.ac.uk/chr9/). The discussions at the meeting are summarized in four sections: 9p, 9cen–q31, 9q32–9q34 and comparative mapping.Many of the posters presented at the meeting were also presented at the ASHG meeting (28–31 October 1998). They are listed here and are published in The American Journal of Human Genetics, vol. 63 (supplement). Abstracts for posters presented only at this meeting are appended to this report.
MtDNA from extinct Tainos and the peopling of the Caribbean
Authors: LALUEZA‐FOX C. , CALDERÓN F. LUNA , CALAFELL F. , MORERA B , BERTRANPETIT J. 
Published: March 2003

Tainos and Caribs were the inhabitants of the Caribbean when Columbus reached the Americas; both human groups became extinct soon after contact, decimated by the Spaniards and the diseases they brought. Samples belonging to pre‐Columbian Taino Indians from the La Caleta site (Dominican Republic) have been analyzed, in order to ascertain the genetic affinities of these groups in relation to present‐day Amerinds, and to reconstruct the genetic and demographic events that took place during the peopling of the Caribbean.Twenty‐seven bone samples were extracted and analyzed for mtDNA variation. The four major Amerindian mtDNA lineages were screened through amplification of the specific marker regions and restriction enzymatic digestion, when needed. The HVRI of the control region was amplified with four sets of overlapping primers and sequenced in 19 of the samples. Both restriction enzyme and sequencing results suggest that only two (C and D) of the major mtDNA lineages were present in the sample: 18 individuals (75%) belonged to the C haplogroup, and 6 (25%) to the D haplogroup. Sequences display specific substitutions that are known to correlate with each haplogroup, a fact that helped to reject the possibility of European DNA contamination. A low rate of Taq misincorporations due to template damage was estimated from the cloning and sequencing of different PCR products of one of the samples. High frequencies of C and D haplogroups are more common in South American populations, a fact that points to that sub‐continent as the homeland of the Taino ancestors, as previously suggested by linguistic and archaeological evidence. Sequence and haplogroup data show that the Tainos had a substantially reduced mtDNA diversity, which is indicative of an important founder effect during the colonization of the Caribbean Islands, assumed to have been a linear migratory movement from mainland South America following the chain configuration of the Antilles.
Novel mutations in the 7‐dehydrocholesterol reductase gene of 13 patients with Smith–Lemli–Opitz syndrome
Authors: JIRA P. E. , WANDERS R. J. A. , SMEITINK J. A. M. , DE JONG J. , WEVERS R. A. , OOSTHEIM W. , TUERLINGS J. H. A. M. , HENNEKAM R. C. M. , SENGERS R. C. A. , WATERHAM H. R. 
Published: March 2003

Smith–Lemli–Opitz syndrome (SLOS) is caused by mutations in the DHCR7 gene leading to deficient activity of 7‐dehydrocholesterol reductase (DHCR7; EC 1.3.1.21), the final enzyme of the cholesterol biosynthetic pathway, resulting in low cholesterol and high concentrations of its direct precursor 7‐dehydrocholesterol in plasma and tissues. We here report mutations identified in the DHCR7 gene of 13 children diagnosed with SLOS by clinical and biochemical criteria. We found a high frequency of the previously described IVS8–1 G > C splice acceptor site mutation (two homozygotes, eight compound heterozygotes). In addition, 13 missense mutations and one splice acceptor mutation were detected in eleven patients with a mild to moderate SLOS‐phenotype. The mutations include three novel missense mutations (W182L, C183Y, F255L) and one novel splice acceptor site mutation (IVS8–1 G > T).Two patients, homozygous for the IVS8–1 G > C mutation, presented with a severe clinical phenotype and died shortly after birth. Seven patients with a mild to moderate SLOS‐phenotype disclosed compound heterozygosity of the IVS8–1 G > C mutation in combination with different novel and known missense mutations.
Coeliac disease: follow‐up linkage study provides further support for existence of a susceptibility locus on chromosome 11p11
Authors: KING A. L. , FRASER J. S. , MOODIE S. J. , CURTIS D. , DEARLOVE A. M. , ELLIS H. J. , ROSEN‐BRONSON S. , CICLITIRA P. J. 
Published: March 2003

Susceptibility to coeliac disease has a strong genetic component. The HLA associations have been well described but it is clear that other genes outside this region must also be involved in disease development. Two previous genome‐wide linkage studies using the affected sib pair method produced conflicting results. Our own family based linkage study of 16 highly informative pedigrees identified 17 possibly linked regions, each of which produced a result significant at p < 0.05 or less.We have now investigated these 17 regions in a larger set of pedigrees using more finely spaced markers. Fifty multiply affected families were studied, comprising the 16 pedigrees from the original genome screen plus 34 new highly informative pedigrees. A total of 128 microsatellite markers were genotyped with an average spacing between markers of 5 cM. Two‐point and three‐point linkage analysis using classical and model free methods identified five potential susceptibility loci with heterogeneity lod scores > 2.0, at 6p12, 11p11, 17q12, 18q23 and 22q13.3. The most significant was a heterogeneity lod of 2.6 at D11S914 on chromosome 11p11. This marker maps to a position implicated in one of the two previous genome scans and taken together these results provide strong support for the existence of a susceptibility locus in this region.
Mitochondrial DNA variability in Poles and Russians
Authors: MALYARCHUK B. A. , GRZYBOWSKI T. , DERENKO M. V. , CZARNY J. , WOŹNIAK M. , MIŚCICKA‐ŚLIWKA D. 
Published: March 2003

Mitochondrial DNA (mtDNA) sequence variation was examined in Poles (from the Pomerania‐Kujawy region; n = 436) and Russians (from three different regions of the European part of Russia; n = 201), for which the two hypervariable segments (HVS I and HVS II) and haplogroup‐specific coding region sites were analyzed. The use of mtDNA coding region RFLP analysis made it possible to distinguish parallel mutations that occurred at particular sites in the HVS I and II regions during mtDNA evolution. In total, parallel mutations were identified at 73 nucleotide sites in HVS I (17.8%) and 31 sites in HVS II (7.73%). The classification of mitochondrial haplotypes revealed the presence of all major European haplogroups, which were characterized by similar patterns of distribution in Poles and Russians. An analysis of the distribution of the control region haplotypes did not reveal any specific combinations of unique mtDNA haplotypes and their subclusters that clearly distinguish both Poles and Russians from the neighbouring European populations. The only exception is a novel subcluster U4a within subhaplogroup U4, defined by a diagnostic mutation at nucleotide position 310 in HVS II. This subcluster was found in common predominantly between Poles and Russians (at a frequency of 2.3% and 2.0%, respectively) and may therefore have a central‐eastern European origin.
Genetic Heterogeneity of Icelanders
Authors: Árnason E. 
Published: March 2003

SummaryRecently statements have been made about a special ‘genetic homogeneity’ of the Icelanders that are at variance with earlier work on blood groups and allozymes. To validate these claims an extensive reanalysis was undertaken of mtDNA variation by examining primary data from original sources on 26 European populations. The results show that Icelanders are among the most genetically heterogeneous Europeans by the mean number of nucleotide differences as well as by estimates of θ parameters of the neutral theory. The distribution of pairwise differences in general has the same shape as European populations and shows no evidence of bottlenecks of numbers in Iceland. The allelic frequency distribution of Iceland is relatively even with a large number of haplotypes at polymorphic frequencies contrasting with other countries. This is a signature of admixture during the founding or history of Iceland. Assumptions of models used to simulate number of haplotypes at sampling saturation for comparing populations are violated to different degrees by various countries. Anomalies identified in data in previous reports on Icelandic mtDNA variation appear to be due to errors in publicly accessible databases. This study demonstrates the importance of basing analyses on primary data so that errors are not propagated. Claims about special genetic homogeneity of Icelanders are not supported by evidence.
Genetic Polymorphisms in the Renin‐Angiotensin System in High‐Altitude and Low‐Altitude Native American Populations
Authors: Rupert J. L. , Kidd K. K. , Norman L. E. , Monsalve M. V. , Hochachka P. W. , Devine D. V. 
Published: March 2003

SummaryCardiovascular disease (CVD) is reportedly less common in high‐altitude native populations than in lowlanders. To some extent, this is due to cultural and demographic factors; however, increased cardiovascular efficiency contributing to hypoxia adaptation may also be involved. Numerous genetic variants have been associated with cardiovascular health. If the decreased incidence of CVD in modern high‐altitude populations reflects selective pressures having favoured the transmission of these alleles in their antecedents, it would be expected that these alleles would be more common in highlanders than in lowlanders. We tested this hypothesis by determining the allele frequencies of five polymorphic loci in genes encoding components of the renin‐angiotensin system (RAS) that have alleles associated with hypertension and cardiovascular disease in a high‐altitude native Andean population, Quechua from the Peruvian altiplano, and in a lowland Amerindian population, Maya from the Yucatan peninsula. The polymorphisms examined were 1) the insertion/deletion polymorphism in intron 16 of the angiotensin converting enzyme (ACE) gene; 2) the A/G2350 transition (ACE‐8) in intron 17 of the ACE gene; 3) the A/C1166 transversion in the 3′ untranslated region of the angiotensin II receptor (type 1) gene (AGTR1); 4) the G/AI9–83 transition in intron 8 of the renin gene (REN); and 5) the T/C704 (Met235Thr) transition mutation in angiotensinogen (AGT).There was no evidence for an over‐representation of the RAS alleles associated with cardiovascular fitness in the high‐altitude Amerindian population when compared to the lowland Amerindian population.
Seven Novel Acid Sphingomyelinase Gene Mutations in Niemann‐Pick Type A and B Patients
Authors: Sikora J. , Pavlu‐Pereira H. , Elleder M. , Roelofs H. , Wevers R. A. 
Published: March 2003

SummaryWe have analyzed acid sphingomyelinase (SMPD1; E.C. 3.1.4.12) gene mutations in four Niemann‐Pick disease (NPD) type A and B patients of Turkish ancestry and in three patients of Dutch origin.Among four NPD type A patients we found two homozygotes for the g.1421C > T (H319Y) and g.3714T > C (Y537H) mutations and two compound heterozygotes, one for the g.3337T > C (F463S) and g.3373C > T (P475L) mutations and the other for the g.84delC (G29fsX74) and g.1208A > C (S248R) mutations.One of the type B patients was homozygous for the g.2629C>T (P371S) mutation. The last two type B patients were homozygotes for the common g.3927_3929delCGC (R608del) mutation.The G29fsX74, S248R, H319Y, P371S, F463S, P475L and Y537H SMPD1 mutations are all novel and were verified by PCR/RFLP and/or ARMS. All of the identified mutations are likely to be rare or private, with the exception of R608del which is prevalent among NPD type B patients from the North‐African Maghreb region. Geographical and/or social isolation of the affected families are likely contributing factors for the high number of homozygotes in our group.
Gene Admixture in the Costa Rican Population
Authors: Morera B. , Barrantes R. , Marin‐Rojas R. 
Published: March 2003

SummaryThe general population of Costa Rica has sometimes been considered to be the product of an amalgamation of groups of diverse origin. To determine the magnitude of accumulated admixture since Spanish colonization, 11 classic genetic markers were analyzed in a total of 2196 individuals originating from five distinct regions of the country. A maximum likelihood approach was used. The proportions of genes of European, Amerindian and African ancestry were found to be 61%, 30% and 9% of the total population, respectively. Variation was observed at a regional level, with an increased European influence in the North (66%) and Central (65%) regions. Meanwhile an increase in Amerindian ancestry was found in the South (38%), and a higher incidence in the contribution of African genes was detected in the coastal regions (13% in the Atlantic and 14% in the North Pacific). A principal component (PC) analysis showed that 76% of the existing variability can be explained by the first two PCs, which is in agreement with the variations observed in the admixture process by geographic area. It has been concluded that the Costa Rican population is truly trihybrid, similar to populations in other Latin American countries; however, it differs from them fundamentally by the proportion of gene flow from ancestral populations.
Using Affected Sibling Pairs to Distinguish the Direct Effect of a Susceptibility Gene and the Indirect Effect of Linkage Disequilibrium
Authors: Lee W.‐C. 
Published: March 2003

SummaryA positive result for a transmission/disequilibrium test (TDT) can occur for two reasons: a) the allele itself is a cause of disease predisposition (direct effect); or b) the allele is in linkage disequilibrium with a disease‐causing gene (indirect effect). A test was proposed based on affected sibling pairs (ASPs) to distinguish between the two. Simulation showed that the test has the correct type I error rate and favourable power (power >50% for 50 ASPs; >75% for 100 ASPs; >85% for 150 ASPs). Making this distinction is important for setting the direction for subsequent studies following a positive TDT result.
Allowing for Genotyping Error in Analysis of Unmatched Case‐Control Studies
Authors: Rice K. M. , Holmans P. 
Published: March 2003

SummaryA commonly‐used method for testing for association between disease and a single‐nucleotide polymorphism (SNP) is to compare the frequencies of the SNP genotypes in a sample of unrelated cases to those in a sample of unrelated controls drawn from the same population (an unmatched case‐control study). A drawback of such a study is that it is impossible to detect genotyping errors, and few methods have been developed to allow for the presence of undetected genotyping errors. In this paper, we obtain analytic formulae for estimates of genotypic relative risks in terms of error probability (e). In general, e will be unknown. We investigate the effect of assuming both correct and incorrect values of e on power and type I error, and also on the genotypic relative risk estimates. The choice of e was found to have no effect on power or Type I error probability (provided a 2df test was used, allowing relative risks of homozygotes and heterozygotes to differ). However, overestimating e in the presence of a true association was found in general to bias relative risk estimates away from the null, with underestimates of e having the opposite effect. Although e is unknown, it may be estimated from an external “validation” study, such as genotyping a sample of unrelated individuals twice and counting the discrepancies. Simulation results suggest that, for such a study, 25 individuals would be sufficient to give approximately unbiased estimates of relative risks.
Segregation Analysis of Prostate Cancer in France: Evidence for Autosomal Dominant Inheritance and Residual Brother‐brother Dependence
Authors: Valeri A. , Briollais L. , Azzouzi R. , Fournier G. , Mangin P. , Berthon P. , Cussenot O. , Demenais F. 
Published: March 2003

SummaryFour segregation analyses concerning prostate cancer (CaP), three conducted in the United States and one in Northern Europe, have shown evidence for a dominant major gene but with different parameter estimates. A recent segregation analysis of Australian pedigrees has found a better fit of a two‐locus model than single‐locus models. This model included a dominantly inherited increased risk that was greater at younger ages and a recessively inherited or X‐linked increased risk that was greater at older ages. Recent linkage analyses have led to the detection of at least 8 CaP predisposing genes, suggesting a complex inheritance and genetic heterogeneity.To assess the nature of familial aggregation of prostate cancer in France, segregation analysis was conducted in 691 families ascertained through 691 CaP patients, recruited from three French hospitals and unselected with respect to age at diagnosis, clinical stage or family history. This mode of family inclusion, without any particular selection of the probands, is unique, as probands from all previous analyses were selected according to various criteria. Segregation analysis was carried out using the logistic hazard regressive model, as incorporated in the REGRESS program, which can accommodate a major gene effect, residual familial dependences of any origin (genetic and/or environmental), and covariates, while including survival analysis concepts.Segregation analysis showed evidence for the segregation of an autosomal dominant gene (allele frequency of 0.03%) with an additional brother‐brother dependence. The estimated cumulative risks of prostate cancer by age 85 years, among subjects with the at‐risk genotype, were 86% in the fathers' generation and 99% in the probands' generation. This study supports the model of Mendelian transmission of a rare autosomal dominant gene with high penetrance, and demonstrates that additional genetic and/or common sibling environmental factors are involved to account for the familial clustering of CaP.
A Note on the Optimal Measure of Allelic Association
Authors: Shete S. 
Published: March 2003

SummaryAssociation of pairs of loci due to departure of gamete frequencies from expected frequencies is called allelic association. This measure is useful for fine‐scale mapping. There are several measures of allelic association in the literature. With the availability of a SNP map, the use of linkage disequilibrium to map genes is one of the central issues in the human genome project. The size of linkage disequilibrium blocks is of considerable interest. In this note, we investigate the statistical properties of a measure which is known to have the strongest theoretical population basis and be least sensitive to the marker allele frequencies. In particular, we have shown that this measure has intuitive appeal and the estimator for this measure has several statistically optimal properties such as consistency, asymptotic unbiasedness and asymptotic efficiency.
Biological characteristics and life tables of Neoseiulus umbraticusChant (Acari, Phytoseiidae) at three constant temperatures
Authors: Kazak C. , Yildiz S. , Sekeroglu E. 
Published: March 2003

AbstractThe development time, survival and fecundity of the generalist predatory mite, Neoseiulus umbraticusChant, were determined at 20, 25, and 30 °C and 65 ± 10 % RH. N. umbraticus females completed development in 9.7, 8.0 and 5.9 days, respectively, using a diet of all life stages of Tetranychus cinnabarinus Boisduval. Total developmental times of males were relatively shorter at 25 and 30 °C than at 20 °C. In general, preoviposition, oviposition, and postoviposition periods of N. umbraticus shortened as temperature increased. The longest survival rate of N. umbraticus of 80.5 days occurred at 20 °C, followed by 67.0 and 57.6 days at 25 and 30 °C, respectively.

Mated females laid an average 0.9, 1.3 and 1.4 eggs per female per day and 33.1, 44.0 and 43.6 eggs over their entire lives at 20, 25 and 30 °C, respectively. The sex ratios of this species were 0.57, 0.57 and 0.54 female (female+male) at 20, 25 and 30 °C, respectively. The intrinsic rate of increase (rm) became greater with rising temperatures from 0.123 at 20 °C to 0.180 at 30 °C. The net reproduction rate (Ro) was highest at 25 °C (25.0 females/female) and lowest at 20 °C (18.8 females/female), while To decreased with increasing temperatures, from 23.8 days at 20 °C to 17.5 days at 30 °C.