bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation of a human cytochrome P‐450 reductase cDNA clone and localization of the corresponding gene to chromosome 7q11.2
Authors: SHEPHARD E. A. , PHILLIPS I. R. , SANTISTEBAN I. , WEST L. F. , PALMER C. N. A. , ASHWORTH A. , POVEY S. 
Published: September 2007

SUMMARYWe have isolated and sequenced cDNA clones that code for rat and human NADPH dependent cytochrome P‐450 reductase. The cDNA coding for the human protein was used to analyse, by Southern blot hybridization, DNA isolated from a panel of 8 independent humanrodent somatic cell hybrids. The results indicate that cytochrome P‐450 reductase is encoded by a single gene (POR) located on human chromosome 7(pter‐q22). Analysis of human metaphase chromosomes by hybridization in situ confirmed the results and refined the localization to 7q11.2. Northern blot hybridization revealed that in human liver the expression of the gene varies by less than 3‐fold between different individuals.
Inbreeding in the Utah Mormons: an evaluation of estimates based on pedigrees, isonymy, and migration matrices
Authors: JORDE L. B. 
Published: September 2007

SUMMARYUsing a computerized genealogical database, inbreeding coefficients were calculated for a sample of 435777 Utah Mormons. The population was divided into ten ten‐year birth cohorts (1846–1945) and 22 geographic subdivisions in order to assess temporal and spatial variation in inbreeding. The average inbreeding coefficient for this population is 0.000 106. The average within‐groups random kinship coefficient is 0.000 312, reflecting consanguinity avoidance. Random kinship matrices were formed by estimating the average kinship within each spatial subdivision and between all pairs of subdivisions. These matrices were compared statistically with kinship matrices previously estimated using migration matrices and isonymy data. The isonymy approach consistently overestimates random and total inbreeding as well as Wright's Fst. This can be attributed primarily to the assumption of monophyletic origin of surnames. The migration matrix method underestimates random inbreeding and Fst. This is due mainly to the assumption that outside immigrants are derived from a genetically homogeneous population. While the absolute values of the kinship coefficients estimated by each method differ substantially, the patterns of between‐groups kinship coefficients given by each method are highly congruent. Logistic and linear regression analyses of 85 235 marriages demonstrate that consanguinity is significantly dependent upon year of marriage, geographic distance between husband's and wife's birthplaces, and the population size of husband's and wife's birthplaces.
Assignment of the human nicotinic acetylcholine receptor genes: the alpha and delta subunit genes to chromosome 2 and the beta subunit gene to chromosome 17
Authors: BEESON D. , JEREMIAH S. , WEST L. F. , POVEY S. , NEWSOM‐DAVIS J. 
Published: September 2007

SUMMARYThe chromosomal assignments of the genes coding for the alpha, beta and delta subunits of the human nicotinic acetylcholine receptor have been determined from a panel of somatic cell hybrids and by direct in situ hybridization. The results localize CHRNA to 2q24‐2q32. CHRNB to 17p11 17p12, and CHRND to chromosome 2q33‐2qter.
Probabilities of orders in linkage calculations
Authors: SMITH C. A. B. 
Published: September 2007

SUMMARYThe present state of linkage estimation procedures is surveyed. When information on linkage between several loci on one chromosome is given in the form of lod scores or likelihoods, a method is developed for finding the probabilities of the different possible orders of the loci, and the distribution of the map distances between them. This depends largely on a Monte Carlo method of integrating the probabilities.
A test based on the exact probability distribution of the χ2 statistic ‐ incorporation into the MASC method
Authors: MULLER B. , CLERGET‐DARPOUX F. 
Published: September 2007

SUMMARYThe MASC method (Clerget‐Darpoux et al. 1988) to test genetic models in HLA associated disease makes use of a test of goodness‐of‐fit on categorized data. This test is composed of a sum of independent χ2s, which are applicable only when expectations in each category are not too small. The commonly used approach to solve this problem is to combine classes in order to raise expectations. This, however, means losing some of the information contained in the data and may decrease greatly the power of discrimination between models. A test based on the exact probability distribution of a test statistic, namely the χ2, has been implemented to avoid this dilemma.
Testing for haplotype sharing by siblings with incomplete information of parental haplotypes
Authors: GREEN J. R. , GRENNAN D. M. 
Published: September 2007

SUMMARYTesting for the inheritance of a disease susceptibility gene by analysis of haplotype sharing among affected siblings has been well established for the case where all four parental haplotypes have been ascertained. This paper presents a modification of a published method to cover the situation where there is incomplete information concerning parental haplotypes and this new test is applied in a worked example.
Kinship structures and migration in the Po Delta
Authors: BARRAI I. , CANELLA R. , BERETTA M. , MAMOLINI E. , BARALE R. , SCAPOLI C. , RAVANI A. 
Published: September 2007

SUMMARYThe kinship analysis of seven genetic systems in the province of Ferrara permits some considerations on the possible chronology of emergence of their polymorphisms in the area. It is proposed that, assuming neutrality of these systems, and under several restrictions, the emergence by migration of the polymorphisms in the seven systems ACP, ESD, GLO, GPT, PGD, PGM1; PGP might have had the following sequence: PGP and GLO and possibly PGD; PGMj and GPT; ACP and ESD. All polymorphisms must be older than the β‐thalassemia polymorphism in the area.
Bayesian methods and optimal experimental design for gene mapping by radiation hybrids
Authors: LANGE K. , BOEHNKE M. 
Published: September 2007

SummaryRadiation hybrid mapping is a somatic cell technique for ordering human loci along a chromosome and estimating the physical distance between adjacent loci. The present paper considers a realistic model of fragment generation and retention. This model assumes that fragments are generated in the ancestral cell of a clone according to a Poisson breakage process along the chromosome. Once generated, fragments are independently retained in the clone with a common retention probability. Based on this and less restrictive models, statistical criteria such as minimum obligate breaks, maximum likelihood, and Bayesian posterior probabilities can be used to decide order. Distances can be estimated by either maximum likelihood or Bayesian posterior means. The model also permits rational design of radiation dose for optimal statistical precision. A brief examination of some real data illustrates our criteria and computational algorithms.
In the multifactorial model of disease transmission, why is the rank correlation sensitive to choice of bivariate distribution?
Authors: HUTCHINSON T. P. 
Published: September 2007

SummaryThe multifactorial model uses a dichotomization (ill vs. well) that occurs in the extreme tail of a bivariate distribution. The crudeness of this is responsible for rank correlation ‐ which is a summary statistic calculated from the whole bivariate distribution ‐ being sensitive to the choice of the bivariate distributional form.
Linkage and association studies with C8A and C8B RFLPs on chromosome 1
Authors: ROGDE S. , GEDDE‐DAHL T. , TEISBERG P. , JONASSEN R. , HØYHEIM B. , OLAISEN B. 
Published: September 2007

SummaryLinkage relations for the C8A and C8B BamHI RFLPs have been investigated. A peak lod score of 4·52 at recombination fraction zero was obtained between the two C8 genes. Combined with our previously obtained linkage data (Rogde et al. 1986) the maximum lod score is 7·53 at recombination fraction zero. The compiled C8‐PGM1 linkage data from this and the previous study gave a maximum lod score of 22·02 at recombination fraction 0·11 (0·07–0·16) with no sex difference. A chromosome 1p reference marker, D1S57, has been applied in this linkage study. A maximum lod score of 5·06 between the C8 cluster and D1S57 at θ= 0·18 (0·11–0·28) was recorded. The linkage analyses and triply informative families gave evidence that the C8 loci are situated about halfway between PGM1 and D1S57 on the short arm of chromosome 1. There was no evidence of allelic association between the C8A and C8B BamHI RFLPs in 62 unrelated haplotypes.
The power of the N‐test of haplotype concordance
Authors: GREEN J. R. , SHAH S. 
Published: September 2007

SummaryThe N‐test of haplotype concordance among siblings affected by some disease under investigation is used to decide whether there is a disease susceptibility gene linked to a marker locus or chromosomal region. The use of this test and appropriate modifications of it is briefly reviewed. The power of the ordinary N‐test is then derived as a function of several parameters. The sample size needed to attain a given power is then derived. Some of the parameters are specified and the required sample sizes are given in tables for different values of the main unknown parameters.
Calculation of genetic identity coefficients
Authors: LANGE K. , SINSHEIMER J. S. 
Published: September 2007

SummaryGenetic identity coefficients define the kind and amount of gene sharing between two relatives at a single locus. Non‐recursive computation of these probabilities depends on cumbersome graph‐tracing algorithms. Closely related to the identity coefficients are certain generalized kinship coefficients which can be computed recursively. The present paper clarifies some ideas of Karigl about how to relate identity coefficients to generalized kinship coefficients.
Linkage analysis of 7 polymorphic markers at chromosome 11p11. 2‐11q13 in 27 multiple endocrine neoplasia type 1 families
Authors: THAKKER R. V. , WOODING C. , PANG J. T. , FARREN B. , HARDING B. , ANDERSON D. C. , BESSER G. M. , BOULOUX P. , BRENTON D. P. , BUCHANAN K. D. , EDWARDS C. R. , HEATH D. A. , JACKSON C. E. , JANSEN S. , LIPS K. , NORUM R. A. , SAMPSON J. , SHALET S. M. , TARGGART R. T. , TAILOR D. , WHEELER M.H. , WOOLLARD P. M. , YATERS J. 
Published: September 2007

SummaryThe multiple endocrine neoplasia type 1 (MEN1) locus has been previously localized to llq13 by combined tumour deletion mapping and linkage studies. Family linkage analysis has defined the locus order as 11cen‐PGA‐(PYGM, MENl)‐(D11S197, D11S146)‐INT2‐11qter, and tumour deletion mapping studies have suggested that the MEN1 locus is proximal to D11S146 but distal to PYGM. In order to establish further the location of MEN1, we have utilized the seven polymorphic DNA probes: D118S88, D11S149, PGA, PYGM, D11S97, D11S146 and INT2, in linkage studies of 339 members (116 affected) from 27 MEN 1 families. Linkage between MEN 1 and 6 of the 7 loci was established, and the highest peak lod scores [Z(θ)] were observed with PYGM and D11S97 at Z(θ) = 13–71, θ= 0.047 and Z(θ) = 13.76, θ= 0.076 respectively. Multilocus analysis suggested the most likely locus order as:11pter‐(D11S288, D11S149)‐11cen‐PGA‐PYGM‐MEN1‐D11S97‐D11S146‐INT2‐11qter. In addition, an examination of individual recombinants indicated a centromeric location of D11S149 in relation to D115288. Thus, the results of our study, which favoured a location of MEN1 proximal to D11S97 and distal to PYGM, have established a panel of recombinants that will facilitate further meiotic mapping studies of the MEN 1 locus.
Correlation between relatives for colorecrtal cancer mortality in familial adenomatous polyposis
Authors: PRESCIUTTINI S. , BERTARIO L. , SALA P. , ROSSETTI C. , LEWONTIN R. C. 
Published: September 2007

SummaryIt has long been realized that age‐specific cancer mortality in Familial Adenomatous Polyposis (FAP) was bimodal, and a theory was proposed in which the involved locus was polymorphic in the general population. After the molecular cloning of the region 5q21, it has been suggested that the phenotypic variability in FAP may be due to the interaction of two loci, one of which is polymorphic. We show that these two hypotheses lead to different predictions of the correlation between relatives for a phenotypic trait, and use colorectal cancer mortality data from the Italian Polyposes Registry to verify them. We conclude that the first of the two is more likely and suggest that the same variation that we observe among the affected subjects is present in the general population. thus causing a significant difference between individuals for colon cancer susceptibility.
Inference of the strength of genotype‐disease association from studies comparing offspring with and without parental history of disease
Authors: TIRET L. , NICAUD V. , EHNHOLM C. , HAVEKES L. , MENZEL H. J. , DUCIMETIERE P. , CAMBIEN F. 
Published: September 2007

SummaryThe association between genetic polymorphisms and a multifactorial disease is generally investigated by case‐control studies. However, inference about the genotype‐disease association can also be drawn from studies comparing offspring having a parental history of disease with offspring having no parental history. In such studies, differences in genotype frequencies between the two groups of offspring will reflect a different transmission of alleles from affected and unaffected parents. We showed that in offspring studies, the odds ratios (ORs) associated with heterozygous and homozygous genotypes are related by the formula: ORhet= (ORhom+1)/2. These ORs depend only on the allele frequencies in affected and unaffected parents, and not on the pattern of genotype‐disease association. Under simple patterns of association, it is possible to infer from the ORs observed among offspring, the expected ORs for the disease. The decrease of power of offspring studies by comparison with classical case‐control studies is evaluated, and an application is given on the association between the apoE polymorphism and coronary heart disease.
Germline rearrangement of MCC and APC detected by pulsed field gel electrophoresis and fluorescent in situ hybridization
Authors: GAYTHER S. , WELLS D. , GULATI K. , CHAPMAN P. , BURN J. , DELHANTY J. D. A. 
Published: September 2007

SummaryPulsed field gel electrophoresis was carried out on lymphocyte DNA obtained from ten patients with the inherited premalignant condition adenomatous polyposis coli and a similar number of control samples to search for large scale molecular rearrangements in the vicinity of the APC locus. DNA from one patient showed a rearranged pattern which was interpreted as evidence for an inversion of approximately 150 kb, changing the transcriptional orientation of the neighbouring MCC gene and bringing it closer to APC. Such an interpretation was supported by fluorescent in situ hybridization data.
An Asp8Asn substitution results in the adenosine deaminase (ADA) genetic polymorphism (ADA 2 allozyme): occurrence on different chromosomal backgrounds and apparent intragenic crossover
Authors: HIRSCHHORN R. , YANG D. R. , ISRANI A. 
Published: September 2007

SUMMARYWe have now determined the molecular genetic basis for the common biochemical polymorphism at the adenosine deaminase (ADA) locus. The ADA*2 allele contains a G to A transition at nt22 (relative to the ATG) that results in substitution of asparagine for aspartic acid at codon 8 (Asp8Asn). Introduction of the nucleotide substitution into an ADA 1 cDNA and transfection into monkey kidney (Cos) cells confirmed that the mutation resulted in expression of an enzyme that comigrated with the naturally occurring ADA 2 allozyme. The substitution of neutral asparagine for anionic aspartic acid is consistent with the more cathodal electrophoretic migration of ADA 2 as compared with ADA 1. The nucleotide substitution was found on at least two different genetic backgrounds, suggesting independent recurrence of the mutation. Consistent with independent recurrence, the G to A transition is at a CpG dinucleotide and represents a type of mutation that occurs with high frequency. We have also unexpectedly identified a probable intragenic crossover in the very large first intron that is rich in repetitive DNA sequences.
The SON gene encodes a conserved DNA binding protein mapping to human chromosome 21
Authors: KHAN I. M. , FISHER R. A. , JOHNSON K. J. , BAILEY M. E. S. , SICILIANO M. J. , KESSLING A. M. , FARRER M. , CARRITT B. , KAMALATI T. , BULUWELA L. 
Published: September 2007

SUMMARYWe report the identification and characterization of a clone for the DNA binding protein SON, which we have isolated from a human keratinocyte cDNA library. Using this clone we have found that the SON gene is expressed in different cell types and that homologous sequences can be detected in vertebrate and insect genomic DNA. Using the polymerase chain reaction (PCR) to amplify SON sequences from a panel of somatic cell hybrids we have assigned the gene encoding human SON to chromosome 21. By use of hybrids containing regions of chromosome 21 the localization has been refined to 21q 22. 1‐q22.2.
Development of a panel of monochromosomal somatic cell hybrids for rapid gene mapping
Authors: KELSELL D. P. , ROOKE L. , WARNE D. , BOUZYK M. , CULLIN L. , COX S. , WEST L. , POVEY S. , SPURR N. K. 
Published: September 2007

SUMMARYWe have assembled a panel of monochromosomal somatic cell hybrids for use in gene mapping. DNA from each individual hybrid was used as a probe on normal human metaphases to identify the human chromosome and any fragments by reverse painting. To test the efficiency of the panel PCR amplification of DNA from the monochromosomal somatic cell hybrid panel was used in combination with human specific oligonucleotide primers to assign α‐catenin (CTNNA1) and p21/WAFl to chromosomes 5 and 6 respectively. These genes were localized further using hybrids containing specific translocations to 5qll‐qter and 6p21 respectively. We also developed primers to enable us to assign 17 ESTs sequenced by the HGMP Resource Centre. The hybrid panel was developed with support of the UK HGMP and the DNA is available to all registered users.
Genetic variation in the COL6A1 region is associated with congenital heart defects in trisomy 21 (Down's syndrome)
Authors: DAVIES G. E. , HOWARD C. M. , FARRER M. J. , COLEMAN M. M. , BENNETT L. B. , CULLEN L. M. , WYSE R. K. H. , BURN J. , WILLIAMSON R. , KESSLING A. M. 
Published: September 2007

SUMMARYGenetic variation in the COL6A1‐COL6A2 gene cluster on chromosome 21 was studied in 113 controls and 58 European families (including control and family subgroups of British/Irish origin) having a child with trisomy 21. There were statistically significant differences among subgroups of trisomic children with and without congenital heart defects (CHD) in distributions of definitive, 3‐RFLP haplotype classes received from their nondisjoining and disjoining parents. Haplotypes received by trisomic children with CHD from their disjoining parents were not a random sample of controls' haplotypes. Analysis of parental single‐RFLP genotypes and linkage disequilibrium patterns confirmed this parent subgroup differed from a random sample of controls. There were no significant differences in parent subgroup genotype distribution at any of nine control loci distributed along chromosome 21q. This sample showed an association between genetic variation in the COL6A1 gene region and congenital heart defects in trisomy 21.
Integration of gene maps: updating chromosome 1
Authors: FORABOSCO P. , COLLINS A. , MORTON N. E. 
Published: September 2007

SUMMARYThe first integrated map of chromosome 1 was published in 1992. We present an updated summary map of 371 loci constructed from a location database that includes physical and genetic data. The summary map subsumes a composite physical location, sex‐specific genetic location, cytogenetic assignment, mouse homology, rank and references to physical maps. The genetic length is 208 cM for the male map, in close agreement with the chiasma map, and 371 cM for the female map. There is evidence for a high level of interference on chromosome 1. The location database comprising both data and analytical software is discussed in relation to alternative approaches and possible enhancements.
Identification of VAV2 on 9q34 and its exclusion as the tuberous sclerosis gene TSC1
Authors: HENSKE E. P. , SHORT M. P. , JOZWIAK S. , BOVEY C. M. , RAMLAKHAN S. , HAINES J. L. , KWIATKOWSKI D. J. 
Published: September 2007

SummaryA novel widely expressed homologue of the VAV oncogene, VAV2 (53% identical residues), has been identified within the critical region for the tuberous sclerosis gene, TSC1, on human chromosome 9q34. By Southern blot analysis, analysis of allele‐specific transcription, and direct sequencing of the VAV2 mRNA/cDNA from patient lymphoblastoid cell lines, we demonstrate that both alleles of this gene are expressed in TSC patients and there are no significant mutations. VAV consists of a novel array of signalling domains and is thought to play an important role in signal transduction in haematopoietic tissues where it is exclusively expressed. VAV2 is likely to serve a similar role more generally in mammalian cells, but is not the TSC1 gene.
Monte Carlo tests for associations between disease and alleles at highly polymorphic loci
Authors: SHAM P. C. , CURTIS D. 
Published: September 2007

SummaryIn an association analysis comparing cases and controls with respect to allele frequencies at a highly polymorphic locus, a potential problem is that the conventional chi‐squared test may not be valid for a large, sparse contingency table. However, reliance on statistics with known asymptotic distribution is now unnecessary, as Monte Carlo simulations can be performed to estimate the significance level of any test statistic. We have implemented a Monte Carlo method for four ‘chi‐squared’ test statistics, three of which involved combination of alleles, and evaluated their performance on a real data set. Combining rare alleles to avoid small expected cell counts, and considering each allele in turn against the rest, reduced the power to detect a genuine association when the number of alleles was very large. We should either not combine alleles at all, or combine them in such a way that preserves the evidence for an association.
Genetic analysis of schizophrenia as an example of a putative multifactorial trait
Authors: PRITCHARD D. J. 
Published: September 2007

SummaryA new method for analysis of multifactorial traits is described which involves mathematical definition of MZ and DZ twin concordances in terms of penetrance and the number of contributory genes. This allows the number of major genes and their joint penetrance to be estimated. Application to familial schizophrenia indicates causation by a single dominant allele, a deduction supported by several treatments of observed risks in other family members. Lifetime empiric risks are analysed in the context of four conditions: genetic predisposition, prenatal trauma, psychological or other trauma in early adult life and possible exacerbation of symptoms associated with close contact with affected family members. Comparative empiric risks for twins and sibs are explained by consideration of coincident gestations, season of birth and the sharing of a chorionic sac and foetal blood supply. The data are consistent with penetrance being complete in homozygotes and generally around 0·33 in heterozygotes, but it increases in additive fashion depending on risk factors associated with the type of relationship with one or more affected family members and factors associated with twinning. The influence of an affected parent is nearly 3 times as great as that of an affected sibling. The population frequency of heterozygotes is deduced to be around 2·6%.