bluuebunny/crossref_metadata_2025_split huggingface dataset:
Standard maps of chromosome 10
Authors: MORTON N. E. , COLLINS A. 
Published: September 2007

SUMMARYTo achieve consensus more exact definitions of genetical maps are required, of which standard, comprehensive and skeletal might be some. A standard genetic map gives distance from pter in centimorgans (cM), uses the international nomenclature for assigned loci, is sex‐specific, and allows as well as possible for interference and typing errors. A standard physical map gives distance from pter in megabases (Mb). A standard map is called comprehensive if it aims to include all syntenic loci, and skeletal if it is limited to loci whose order is well supported. Loci with established order are called skeletal, and are used to define regional assignments of other loci.These principles are illustrated using the CEPH data for chromosome 10. Map lengths by multiple 2‐point analysis under supported interference are in good agreement with other evidence, but multipoint mapping gives a substantial overestimate. There are currently 21 loci in the skeletal genetic map and 40 loci in the comprehensive genetic map. From these data, cytogenetic assignments, and partial genetic maps the physical location has been estimated for 85 loci. MEN2A is in a region close to the centromere in which male recombination per megabase is much reduced. Order of DNA markers in this densely mapped region has not been determined, and therefore the exact location of MEN2A is uncertain, although it is likely to lie between D10S34 and D10S30 and close to D10S11.
The linkage detection problem
Authors: EDWARDS J. H. 
Published: September 2007

SUMMARYLinkage data in man are usually analysed on families lacking a full set of grandparents on the assumption that there is one locus relating to an abnormal phenotype, the test locus. The basic problems of establishing linkage of this locus to another locus, the marker locus, with a defined likelihood and of estimating the recombination fraction were resolved by Morton(1955). However, the likelihood ratio derived after estimating the most likely recombination fraction is widely misunderstood to be a direct measure of the likelihood of linkage while the bias of estimates conditional on some likelihood criterion derived from the same data is usually ignored. Since data are limited this tolerance of excessive confidence in detecting linkages and a consistent tendency to underestimate recombination fractions is justified but the expected errors are not small and they are readily magnified when multiple loci are involved.Multiple markers provide further opportunities for detecting false linkages although the corrections required are known. The problems imposed by multiple loci at which mutations lead to a common phenotype have so far had little consideration. As most proteins are multimers whose units are not necessarily coded for by neighbouring loci, and as disturbances to any of several enzymes acting in series may lead to similar consequences, the assumption of a one‐to‐one relationship between a locus and a phenotype will usually be wrong.
Spinocerebellar ataxia (SCA1) in two large Italian kindreds: evidence in favour of a locus position distal to GLO1 and the HLA cluster
Authors: FRONTALI M. , IODICE C. , LULLI P. , SPADARO M. , CAPPELLACCI S. , GIUNTI P. , MALASPINA P. , MORELLINI M. , MOROCUTTI C. , NOVELLETTO A. , PERSICHETTI F. , TRABACE S. , ANASTASI R. , TERRENATO L. 
Published: September 2007

SUMMARYTwo large Italian pedigrees with HLA‐linked spinocerebellar ataxia (SCA1) were typed for HLA‐A, ‐B and ‐DR as well as for markers either distal (F13A, D6S8) or proximal (D6S29, GLOl) to HLA. Pairwise linkage analyses of SCA1 vs. HLA‐A, ‐B and ‐DR showed peak lodscores of 5‐3, 5‐6 and 3‐3 respectively at 7 % recombination. Negative lodscores significantly excluded linkage with F13A at less than 5% and with GLOl at less than 10%. The lodscores with D6S8 and D6S29 had only low peaks.Recombination events in the two pedigrees and the estimated genetic distances of SCAl from GLOl and HLA favour the hypothesis of a SCA1 location distal to both of them. An order cen‐GLOl‐HLA‐SCAl‐tel appears therefore most likely with present data. These results are discussed in relation to previous reports placing SCA1 distal to HLA in two families and proximal in another.
A new genetic polymorphism in human platelet polypeptides detected by two‐dimensional electrophoresis
Authors: KAJII E. , IWAMOTO S. , OMI T. , IKEMOTO S. 
Published: September 2007

SUMMARYWe describe a new genetic polymorphism of human platelet polypeptide, detected by two‐dimensional polyacrylamide gel electrophoresis followed by silver‐staining. The polymorphism was tentatively designated thrombocyte B (ThB) with a molecular weight of 34 k Da and isoelectric point of 4‐7‐4‐8. In this polypeptide, three different electrophoretic types (1‐1, 1‐2, 2‐2) were identified. Family and population studies indicate that the three phenotypes of the polypeptide are determined by two common alleles at a single autosomal locus. In a Japanese population, the gene frequency of ThB 1/ThB 2 was 0.74/0.26. The ThB polypeptide was not found in other blood cells and decreased or disappeared during the preparation or storage of platelets.
Assignment of the Hepatocyte Growth Factor (HGF) to chromosome 7q22‐qter
Authors: LAGUDA B. , SELDEN C. , JONES M. , HODGSON H. , SPURR N. K. 
Published: September 2007

SUMMARYThe hepatocyte growth factor (HGF) is thought to be important in the growth of hepatocytes during normal foetal liver growth and following liver damage. The human gene encoding HGF has been mapped to chromosome 7 and shown to be localized in the region q22‐qter.
Chromosomal assignment of human phenol and bilirubin UDP‐glucuronosyltransferase genes (UGT1A‐subfamily)
Authors: MOGHRABI N. , SUTHERLAND L. , WOOSTER R. , POVEY S. , BOXER M. , BURCHELL B. 
Published: September 2007

SummaryDNA probes were prepared from the 5′ ‐terminal portion of four cDNA clones encoding human phenol and bilirubin UDP‐glucuronosyltransferases (UGTs). An additional sequence common to all four clones was isolated from the 3′ ‐terminal portion of one of the clones (UGT1A1).The four specific and the one common DNA sequences were used as probes on a panel of 16 human‐rodent somatic cell hybrid DNAs by Southern‐blot analysis. The results obtained indicate that all four cDNA clones are encoded by gene(s) located on human chromosome 2.
Carrier detection of deletions of the Hunter gene by in situ hybridization
Authors: STONE S. , ADINOLFI M. 
Published: September 2007

SummaryDeficiency of the lysosomal enzyme α‐iduronate sulphate sulphatase (IDS) causes the clinical manifestations of Hunter syndrome, an X‐linked condition. In about 30% of male patients, the disease is due to a major deletion. Using a non‐isotopic in situ hybridization (NISH) method, and a yeast artificial chromosome (YAC) probe, the Hunter gene was mapped to the terminal region of the human X chromosome, close to the Xq28 band.The NISH procedure was then applied to investigate the carrier status of female relatives of a Hunter patient known to have a deletion of the IDS gene.Unequivocal evidence that two female relatives were carriers of the deletion was obtained, demonstrating that the NISH method is a valuable diagnostic tool in genetic counselling of families with Hunter patients.
Algorithms for a location database
Authors: MORTON N. E. , COLLINS A. , LAWRENCE S. , SHIELDS D. C. 
Published: September 2007

SummaryThe algorithms that drive the Idb location database are described. The program captures data on genetic and physical maps and combines information from different sources into a summary map. To assure portability it was developed in Fortran on a SUN SPARCStation under Unix. The algorithms, which combine rule‐based seriation with a minimum deviance bootstrap, allow investigators and chromosome committees to produce a composite location in Mb that integrates partial maps. The program and manual are now available from the authors.
The genes coding for phosphoenolpyruvate carboxykinase‐1 (PCK1) and neuronal nicotinic acetylcholine receptor α4 subunit (CHRNA4) map to human chromosome 20, extending the known region of homology with mouse chromosome 2
Authors: PILZ A. J. , WILLER E. , POVEY S. , ABBOTT C. M. 
Published: September 2007

SummaryThe mouse genes for cytosolic phosphoenolpyruvate carboxykinase‐1 (Pck‐1) and neuronal nicotinic acetylcholine receptor a4 subunit (Acra‐4) both map to distal chromosome 2 (Siracusa et al. 1989; Bessis et al. 1990). We have utilized Southern blot analysis on human/rodent somatic cell hybrids to map the human homologues of both of these genes, PCK1 and CHRNA4, to human chromosome 20.
Mitochondrial DNA polymorphisms in Khoisan populations from Southern Africa
Authors: SOODYALL H. , JENKINS T. 
Published: September 2007

SummaryMitochondrial DNA (mtDNA) restriction fragment length polymorphisms (RFLPs) were investigated in 95 individuals, consisting of 49 San (‘Bushmen’) and 46 Nama (‘Hottentot’) individuals from Namibia, using the restriction enzymes HpaI, BamHI, HaeII, MspI, AvaII and HincII. Six of the eleven types found in the pooled Khoisan sample are shared, albeit at varying frequencies, suggesting that both the San and Nama have evolved from a recent common ancestor. However, San and Nama groups differ appreciably, in particular, type 3‐2 (3‐1‐1–2‐2‐2) was found in 7/49 Sekele and 25/46 Nama (χ2[1]= 15·3, P= 9·17 × 10‐5). In addition, type 4 makes up 428 % of the types found in the San, and is not found in the Nama group. This suggests that the San and Nama have evolved along separate lineages, with little gene flow between them, following their proposed separation from a common Khoisan ancestor. Type 7‐2 (3‐1‐1‐1‐1‐2), most common in Negroid populations, is found at a higher frequency in the San (20·4%) than the Nama (6·5%), suggesting that miscegenation involving Negroid females and San males is more common than that between Negroid females and Nama men. The higher frequency of type 21‐2 (2‐1‐1‐1–2‐2) in the Nama (13%) than in the San (4·1%), may be attributable to gene flow from the Dama into the Nama, consistent with the consequences of enslavement of the Dama by the Nama.
Segregation and linkage analysis in five manic depression pedigrees excludes the 5HT1a receptor gene (HTR1A)
Authors: CURTIS D. , BRYNJOLFSSON J. , PETURSSON H. , HOLMES S. , SHERRINGTON R. , BRETT P. , RIFKIN L. , MURPHY P. , MOLONEY E. , MELMER G. , GURLING H. M. D. 
Published: September 2007

SummaryFive kindreds selected through probands attending an Icelandic hospital were recruited for linkage studies of manic depression. The rates of affection were equal for males and females and the age of onset appeared to be predominantly in early adult life, since prevalence did not rise appreciably with age. A complex segregation analysis was performed using the computer program pointer to obtain maximum likelihood estimates of the contributions to liability from multifactorial transmission and a single major locus. Likelihood ratios between models supported a role for a single major locus which was dominant and had moderately high penetrance with, in the case of unipolar illness, additional multifactorial transmission. The bestfitting parameters were used to devise a transmission model for linkage analysis. Three markers on chromosome 5 were studied, at D5S76, D5S6 and D5S39. Strongly negative lod scores were obtained which were less than ‐2 over a distance of 40 cM, which included the region to which the gene for the 5HT1a receptor has been mapped.
Bayesian inference in multipoint gene mapping
Authors: STEPHENS D. A. , SMITH A. F. M. 
Published: September 2007

SummaryThe problem of rodering and mapping genes on the basis of recombinant data and radiation hybrid data is formulated as a problem of Bayesian inference for an unknown permutation. The challenging computational problems posed by this approach are shown to be resolvable using Markov chain Monte Carlo methods.
Molecular genetic evidence for the delineation of more severe form of familial adenomatous polyposis which results from fresh mutation
Authors: REES M. , LEIGH S. E. A. , DELHANTY J. D. A. , Bowles L. , TALBOT I.C. 
Published: September 2007

SummaryFamilial adenomatous polyposis, an inherited pre‐malignant condition, is caused by mutation in the adenomatous polyposis coli (APC) gene at chromosome 5q22. The lifetime risk of carcinoma approaches loo%, with an average age at death from cancer of 40 years, allowing most patients to complete reproduction. Since there is no evidence for a rising incidence, this is at variance with an apparently high mutation rate. We present evidence for the delineation of a severe form, which hitherto has largely been maintained by fresh mutation. An atypically high frequency of loss of heterozygosity at chromosome 5q22 in small adenomas correlated with an early age of onset or malignancy in two patients, both due to fresh mutation. In both cases, the mutation in APC was shown to be a commonly occurring deletion, leading us to postulate the co‐existence of a modifying gene.
Barriers to gene flow estimated by surname distribution in Italy
Authors: ZEI G. , BARBUJANI G. , LISA A. , FIORANI O. , MENOZZI P. , SIRI E. , CAVALLI‐SFORZA L. L. 
Published: September 2007

SummarySurname distributions were studied in order to reconstruct human migration patterns. Zones of sharp change in surname frequencies ‐ presumably barriers to gene flow ‐ were detected by the statistical technique of wombling (Barbujani et al. 1989), using data from consanguineous marriages (1910‐64) collected from 280 Italian dioceses which we grouped into 80 provinces. The 28 observed surname boundaries were compared with physical (geographical) and cultural (linguistic) barriers, and with boundaries detected from distributions of 57 alleles in the same territorial subdivisions. Genetic and surname boundaries had similar locations, as expected given the analogy in the inheritance mechanism of genes and surnames. Physical barriers seemed to be the main cause of gene flow reduction. However, cultural factors alone (e.g. linguistic ones) also determined barriers that delimited areas of homogeneous gene (and surname) frequency probably due to increased endogamy. The observed similarity between spatial patterns of surnames, genes and languages supports the hypothesis of the co‐evolution of genetic and linguistic variation.
Rh null phenotypes are not due to a gross deletion and can occure on different Rh genetic backgrounds
Authors: CARRITT B. , BLUNT T. , AVENT N. , DANIELS G. , STEERS F. 
Published: September 2007

SummaryAlu element‐primed PCR was performed on genomic clones containing human RH blood group genes. When used as a probe, the Alu PCR product detected a restriction fragment‐length polymorphism which is in complete linkage disequilibrium with the Rh C/c serological polymorphism, irrespective of the Rh D or E serological type it is coupled with. This provides the opportunity to type individuals for their RH C gene directly at the DNA level. RFLP analysis of two individuals with the amorph Rh null phenotype revealed that in one case this phenotype occurred on an RH C background, whereas in the other it was on an RH c background. Taken together these results indicate that the Rh C/c polymorphism has arisen only once, but that the amorph Rh null phenotype, although exceedingly rare, is the result of at least two independent mutations.
Extimating the correlation among siblings
Authors: KEEN K. J. 
Published: September 2007

SummaryBeginning with Galton, Various authors have proposed non‐iterative estimators of the correlation coefficient that measure the degree of similarity among siblings. However, these extimators lose efficiency appreciable for certain ranges of values of the correlation coefficient. An estimator formed by an algebraic combination of two non‐iterative extimators based on Smith (1957) is shown by simulation to be nearly full efficent for teh full range of values of the coefficent. A new estimator given by the best linear combination of these extimators offers a practical improvement for large values of the coefficent. The discussion conceludes with an example.
Mapping of RXRB to human chromosome 6p21. 3
Authors: FITZGIBBON J. , GILLETT G. T. , WOODWARD K. J. , BOYLE J. M. , WOLFE J. , POVEY S. 
Published: September 2007

SummaryRetinoid X Receptor beta (RXRB) is a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the effects of retinoic acid (RA). We have confirmed the localization of RXRB to chromosome 6 and we have mapped the gene to chromosome 6p21. 3‐p21.1 by PCR amplification of 5′ untranslated sequence in panels of rodent‐human somatic cell hybrids and to 6p21.3 by fluorescent in situ hybridization.
Sex ratio and natural selection in humans: a comparative analysis of two Caucasian populations
Authors: ULIZZI L. , ZONTA L. A. 
Published: September 2007

SummaryIn the course of the last century industrialized countries have experienced significant changes in mortality rates. Since the sex ratio of a population may be considered a function of, among other factors, differential mortality in the two sexes, it is expected to correlate with changes in sex‐specific mortality rates.In this paper secular changes in the sex ratio at birth and after the action of relevant components of early selection (stillbirth, mortality within the first month and within the first year of life) have been studied in the Italian and in the USA White populations.The results can be summarized as follows.(i) In the past, extra male‐specific mortality appeared to reduce the relatively large values of the sex ratio observed at birth, and this held true in both populations.(ii) In more recent times, male‐specific mortality has been decreasing in all age groups, and the sex ratios before and after the action of early selection now tend to identical values.Therefore, it can be envisaged that in the near future the sex ratio observed at birth will be maintained up to the reproductive age. If the reproductive value is stabilized by natural selection, as is likely, new relationships between sex ratio and selection may be expected to develop in a relatively short time.
The effect of variation in the apolipoprotein B gene on plasma lipid and apolipoprotein B levels I. A likelihood‐based approach to cladistic analysis
Authors: HALLMAN D. M. , VISVIKIS S. , STEINMETZ J. , BOERWINKLE E. 
Published: September 2007

SUMMARYA new method is described for employing family data to test for significant haplotype effects on continuously distributed variables, using likelihood‐ratio tests of linear models in which haplotype effects are parameterized and familial correlations taken into account. The method is applied to the apolipoprotein B (Apo B) gene, using 5 polymorphisms (Insertion/deletion, Bsp1286I,XbaI,MspI,EcoRI) to define haplotypes in 121 French nuclear families. Eleven haplotypes were found, five of which, combined, account for over 95% of the sample. A haplotype phylogeny is proposed, and is used to define a nested set of models for testing the effects of Apo B variation on total‐, low‐density‐lipoprotein (LDL)‐, and high‐density ‐lipoprotein (HDL)‐cholesterol, triglyceride, and Apo B levels. Apo B haplotype effects account for about 10% of the genetic variance and 5% of the total variance in HDL‐cholesterol and triglyceride levels. Clusters of evolutionarily‐related haplotypes with similar phenotypic effects are identified for HDL‐cholesterol and triglycerides. Single haplotypes with statistically significant effects are identified for cholesterol, LDL‐cholesterol, and Apo B levels.
Consanguineous marriage in Turkey and its impact on fertility and mortality
Authors: TUNÇBÍLEK E. , KOC I. 
Published: September 2007

SUMMARYTurkey has a high rate of consanguineous marriage (21·1 %), indicating strong preference for this traditional form of marital union. Social and cultural factors are especially important in marriages between first and second cousins. Fertility is high, the closed birth interval is long, and the sterility rate is low among these couples. Post‐neonatal, infant and under‐5 mortalities are high in first cousin unions by comparison with non‐consanguineous marriages. According to the results of the study, first cousin marriage is a significant determinant underlying the high total fertility and infant mortality rates in Turkey.
Estimating multipoint recombination fractions
Authors: SMITH C. A. B. , STEPHENS D. A. 
Published: September 2007

SUMMARYThe likelihood in linkage investigations can be expressed as a polynomial in the relevant recombination fractions. With polymorphic characters, this can be reduced to a product of separate factors for female and male recombinations, with only mild loss of information. With three generation data the polynomials take a specially simple form. Algorithms are given for finding maximum likelihood estimates and their standard errors.
An integrated map of chromosome 9
Authors: COLLINS A. , FORABOSCO P. , LAWRENCE S. , MORTON N. E. 
Published: September 2007

SUMMARYAn integrated map of 211 loci on chromosome 9 is presented for which 198 loci have genetic locations. The results of the analysis indicate very strong interference for the chromosome and positional variations in recombination rates, most extreme in the male map where there is an excess of recombination near the p telomere and a marked suppression of recombination in a large region that includes the centromere.
Linkage detection under heterogeneity and the mixture problem
Authors: CHIANO M. N. , YATES J. R. W. 
Published: September 2007

SummaryLinkage analysis has contributed to the localization of many human disease genes. The presence of locus heterogeneity reduces statistical power and can prejudice the detection of linkage if the analysis assumes homogeneity. Nevertheless, mixed genetic models are not routinely used in gene searches. The null distribution of the test statistic is not uniquely defined. In this paper, a transformation is used to determine an approximate asymptotic distribution of the test statistic under a mixture model. The equivalent critical values of the test are computed and the performance of the test under various levels of heterogeneity and family size is investigated. For gene searches, we recommend the routine use of an admixture model with a critical lod score of 3·44.
Estimation of quantitative genetic parameters under non‐normal models
Authors: ANDRADE MARIZA de 
Published: September 2007

SummaryIn traditional quantitative genetics, the relationship between the observed value of a quantitative trait in a set of families and its genetic and environmental contributions can be described as a linear additive relationship. Generally, it is assumed that the genetic and environmental effects are independent and normally distributed. Consequently, the quantitative trait also has a normal distribution. However, there are some situations where the phenotype does not follow the normal distribution. To deal with this problem the author suggests the families of distributions that belong to the Johnson Translation System (JTS). As an example, two dependent quantitative traits, weight and height, are investigated assuming that they have a lognormal and normal distribution, respectively. Computational methods for estimating the genotypic variances and covariances are presented.