bluuebunny/crossref_metadata_2025_split huggingface dataset:
An extended transmission/disequilibrium test (TDT) for multi‐allele marker loci
Authors: SHAM P. C. , CURTIS D. 
Published: September 2007

SUMMARYThe transmission/disequilibrium test (TDT) was recently introduced by Spielman et al. (1993) as a test for linkage and linkage disequilibrium. The test is based on the unequal probability of transmission of two different marker alleles from parents to affected offspring, when the marker locus and the hypothetical disease locus are linked and are in linkage disequilibrium. The probabilities of marker allele transmission to affected offspring conditional on parental genotype have been derived by Ott (1989) for a biallelic marker and a recessive disorder with no phenocopies. Here, we derive the transmission probabilities for a multi‐allele marker locus and a generalized single locus disease model in a random sample of affected individuals from a randomly mating population. The form of these transmission probabilities suggests an extension of the TDT to multi‐allele marker loci, in which the alternative hypothesis is restricted to take account of the likely pattern of unequal transmission when the recombination fraction is near 0. We show how our extended TDT can be implemented by standard software for logistic regression, although we have also written our own program which is available on request. We have evaluated the approximate power of the test under a range of realistic assumptions, and it appears that the test will often have good power when linkage disequilibrium is strong and if the disease is recessive.
REPORT on the Fourth International Workshop on Chromosome 9: held at Williamsburg, Virginia, USA, April 23–25, 1995
Authors: PERICAK‐VANCE M. A. , BALE A. E. , HAINES J. L. , KWIATKOWSKI D. J. , PILZ A. , SLAUGENHAUPT S. , WHITE J. A. , EDWARDS J. H. , MARCHUK D. , OLOPADE O. I. , ATTWOOD J. , POVEY S. 
Published: September 2007

SUMMARYThe Fourth International Workshop on Chromosome 9 was a highly successful endeavor in terms of the growth of the map, both genetic and physical, the amount of data entered into GDB, and the continued comradeship in the sharing of data and resources that was exemplified. SIGMA remained a stable and valuable part of the chromosome 9 mapping effort. A new subsection outlining the morbid anatomy of chromosome 9 was included. Finally, specific goals were set for the community to aim for over the upcoming months. These included extending the information about the ease of use of genetic markers, and coordinating across numerous groups the meiotic breakpoint mapping of many microsatellite markers. Workshop files are available by anonymous ftp from ftp.gene.ucl.ac.uk (128.40.82.1) in the subdirectory /pub/c9workshop/1995, or by using a World Wide Web browser (such as Mosaic or Netscape) via the Chromosome 9 Home Page (at the URL http:www.gene.ucl.ac.ukchr9home.html).
An extension of the Maximum Lod Score method to X‐linked loci
Authors: CORDELL H. J. , KAWAGUCHI Y. , TODD J. A. , FARRALL M. 
Published: September 2007

SUMMARYThe Maximum Lod Score method for affected relative‐pair analysis, introduced by Risch, is a powerful method for detecting linkage between an autosomal marker locus and disease. In order to use the method to detect linkage to markers on the X‐chromosome, some modification is necessary. Here we extend the method to be applicable to X‐chromosomal data, and derive genetic restrictions on the haplotype‐sharing probabilities analogous to the ‘possible triangle’ restrictions described by Holmans for the autosomal case. Size criteria are derived using asymptotic theory and simulation, and the power is calculated for a number of possible underlying models. The method is applied to data from 284 type 1 diabetic families and evidence is found for the presence of one or more diabetogenic loci on the X‐chromosome.
Characterization of a dinucleotide repeat in the 92 kDa type IV collagenase gene (CLG4B), localization of CLG4B to chromosome 20 and the role of CLG4B in aortic aneurysmal disease
Authors: JEAN P. L. ST , ZHANG X. C. , HART B. K. , LAMLUM H. , WEBSTER M. W. , STEED D. L. , HENNEY A. M. , FERRELL R. E. 
Published: September 2007

SummaryProteolytic imbalance may play a role in the pathogenesis of abdominal aortic aneurysms (AAA). CLG4B, which encodes the 92‐kDa form of type IV collagenase, is a candidate gene for AAA. We genotyped a polymorphic dinucleotide repeat in the 5′ flanking region of CLG4B in 94 unrelated Caucasian controls and in 127 unrelated Caucasian AAA cases. Eight alleles were detected in 188 control chromosomes with an observed heterozygosity of 0·68. There was no significant difference in allele distribution between cases and controls. We genotyped the dinucleotide repeat in 10 CEPH reference pedigrees and performed pairwise linkage analysis with markers on each of the 22 human autosomes. Lod scores between 10·45 and 20·29 were observed with markers spanning chromosome region 20q11.2‐q13.1. Further support for assignment of CLG4B to chromosome 20 was provided by analysis of human‐rodent somatic cell hybrids. This work describes a highly polymorphic marker in the CLG4B gene and assigns this gene to chromosome 20.
Haplotype comparison in fresh mutation cases of adenomatous polyposis coli due to deletion AAAGA at codon 1309
Authors: DELHANTY J. D. A. , TSIOUPRA K. 
Published: September 2007

SummaryTo determine whether the common 5 base pair deletion (δAAAGA) at codon 1309 of the APC gene occurs preferentially on a particular haplotype background, three intragenic polymorphisms were typed using the polymerase chain reaction in ten patients with this deletion as the disease‐causing mutation. Each case was due to fresh mutation. The data obtained provide no evidence in support of a preferential haplotype predisposing to this mutation.
Nuclear DNA polymorphism in a Mandenka population from Senegal: Comparison with eight other human populations
Authors: POLONI E. S. , EXCOFFIER L. , MOUNTAIN J. L. , LANGANEY A. , CAVALLI‐SFORZA L. L. 
Published: September 2007

SummaryA large and ethnically well defined Mandenka sample from Senegal is analysed for 80 nuclear DNA RFLPs, and compared with eight previously studied human populations. A high level of genetic diversity is found in this sample, comparable to that observed in two African Pygmy samples, but lower than that of a European sample. High population variation is observed for most markers. A neutrality test reveals that the markers used in this study can be considered as neutral. A high correlation is found between genetic and geographic distances (r= 0·62), suggesting that geography does also affect long range population genetic relationships and is an important factor behind differentiation among human populations.
Human mitochondrial DNA variation and the origin of Basques
Authors: BERTRANPETIT J. , SALA J. , CALAFELL F. , UNDERHILL P. A. , MORAL P. , COMAS D. 
Published: September 2007

SummaryThe hypervariable segment I of the control region of the mtDNA (positions 16024–16383) was PCR‐amplified from mouth scrape and hairs and sequenced in 45 unrelated individuals of pure matrilineal Basque descent. Twenty‐seven different sequences were found, of which 21 are unique to the Basques. The allelic partition observed, together with resampling experiments, suggested that much more variation remained to be discovered.The mean pairwise difference in number of nucleotides between individuals was 3·15, a very low value. Moreover, the number of steps for the most parsimonious tree is very low compared to the number of different sequences. Both findings suggest that the Basque population was founded by a few lineages that diverged in a short time span. The number of nucleotide differences between individuals was shown not to be influenced by the distance between their birthplaces, thus validating the sampling strategy used a posteriori.The pairwise difference distribution agreed well with the three‐parameter model proposed by Rogers & Harpending (1992). The parameter estimates found for the Basques implied that a demographic expansion (or perhaps two, given the bimodal shape of the distribution) took place sometime between 14500 and 42000 BP which is in agreement with archaeological data.Our sample was compared to other populations for which D‐loop sequences were available through the Nei & Miller (1990) distance. In a neighbour‐joining tree, all the Caucasoid samples, including the Basques, appeared tightly clustered, whereas African samples were the most distant to the Caucasoids and also the most heterogeneous. Although classical markers, such as blood groups and protein polymorphisms, clearly separate the Basques (and the Sardinians) from other European populations, this distinctiveness was not found using D‐loop sequences.
The genetic structure of a province as revealed by surnames and HLA genes: potential utility in transplantation policy
Authors: GUGLIELMINO C. R. , DE SILVESTRI A. , MARTINETTI M. , DAIELLI C. , SALVANESCHI L. , CUCCIA M. 
Published: September 2007

SUMMARYThe combined use of surnames, which simulate selectively neutral genetic markers, and HLA genes may constitute a useful tool for the genetic survey of a small area. We found a coincidence between HLA genetic structure and surname ‘selectively neutral’ pattern, in an Italian province, although HLA genes indicate a more pronounced genetic isolation for one particular subregion of the province. The patchiness of HLA allele distribution that is sometimes created by drift and/or selection can be used as the basis both of anthropological and of epidemiological studies. The creation of genetic maps of relatively small areas may also constitute a tool for the selection of bone marrow donors.
A note on the combination of estimates of a recombination fraction
Authors: LIN S. , SPEED T. P. 
Published: September 2007

SUMMARYA number of ways of combining two or more independent estimates of the same recombination fraction can be found in the literature. We revisit this topic in the context of human gene mapping, and explore the value of transforming the recombination fraction to a new parameter whose log‐likelihood function is more nearly quadratic. It is shown that the arcsine of the cube‐root is one such function. These observations lead naturally to a way of summarizing and combining the summarized set of log‐likelihood functions of a common recombination fraction. This idea is illustrated using pedigree data concerning six loci on chromosome 10 from the CEPH consortium. A comparison is also made with the method of summarizing and combining using ‘equivalent numbers’ of recombinants and informative meioses.
Identification of an E689K substitution as the molecular basis of the human acid α‐glucosidase type 4 allozyme (GAA*4)
Authors: HUIE M. L. , MENAKER M. , MCALPINE P. J. , HIRSCHHORN R. 
Published: September 2007

SUMMARYWe have identified the molecular basis of the GAA*4 allozyme as a G to A transition at nt2065 which predicts the substitution of glutamic acid by lysine at codon 689 (E689K). The conclusion that this change represents the molecular basis of the GAA*4 allozyme is based on 1) presence of the G2065A in homozygosity in a known GAA*4 homozygote, 2) transient expression studies showing normal enzyme activity expressed by cDNA containing the G2065A transition and 3) isoelectric focusing studies showing a more cathodal pattern for the expressed product as compared to the common GAA*1, analogous to the patterns seen in normal and known GAA*4 lymphoid cells.
Dynamic mutation loci: allele distributions in different populations
Authors: RICHARDS R. I. , CRAWFORD J. , NARAHARA K. , MANGELSDORF M. , FRIEND K. , STAPLES A. , DENTON M. , EASTEAL S. , HORI T.‐A. , KONDO I. , JENKINS T. , GOLDMAN A. , PANICH V. , FERAKOVA E. , SUTHERLAND G. R. 
Published: September 2007

SUMMARYTo assess the relative contributions of trans‐acting factors (replication and repair functions) and cis‐acting elements (repeat and flanking DNA composition) to the mechanism of trinucleotide repeat sequence mutation we have analysed the distribution of copy number polymorphisms at 12 loci associated with dynamic mutations in 15 populations of different ethnic origins. Genome wide instability of repeats in a particular population would be evidence of trans‐acting factor instigation of the mutation process, whereas instability at a particular locus (perhaps even in several populations) would be evidence that the composition of the particular locus was the most significant factor contributing to mutation. The FRA16A locus is highly polymorphic in only the European population. Some other loci exhibit distinct distributions of alleles between different populations. Therefore sequences in the vicinity of the repeat ‐ the cis component of a particular locus ‐ appear(s) to be more important in the mutation mechanism than sporadic genome‐wide instability induced by trans‐acting factors such as the DNA mismatch repair enzymes.
The negative heritability of neonatal jaundice*
Authors: HALDANE J. B. S. 
Published: September 2007

SummaryIn the case of neonatal jaundice due to the human D antigen, mothers who have been jaundiced cannot bear a jaundiced child, and fathers who have been jaundiced beget fewer jaundiced sons than those who have not. Other characters may have a similar negative heritability.
Distribution of tandem repeat polymorphism within minisatellite MS621 (D5S110)
Authors: ARMOUR J. A. L. , CROSIER M. , JEFFREYS A. J. 
Published: September 2007

SummaryThe minisatellite MS621 (D5S110) is a highly polymorphic tandem repeat locus which maps to the distal region of human chromosome 5p. Major repeat unit variants at D5S110 differ not by base substitutions but by differences in the repetition of an 11 bp sequence motif found within each repeat. The two major classes of repeat unit thus contain two (‘ dimeric ’= D‐type) or three (‘ trimeric ’= T‐type) copies of this short motif. Mapping the distribution of these D‐ and T‐type repeat units within alleles has allowed the analysis of the structural basis of allelic variation and of one de novo mutation. In contrast to previous studies of some other highly polymorphic minisatellites, this analysis provided no clear evidence for polarized variability at D5S110.
Two additional polymorphisms within the hypervariable MUC1 gene: association of alleles either side of the VNTR region
Authors: PRATT W. S. , ISLAM I. , SWALLOW D. M. 
Published: September 2007

SummaryThe gene MUC1 codes for a mucin‐type glycoprotein and like most of the other mucin genes shows variable number tandem repeat (VNTR) polymorphism within the coding region. A polymorphism due to a G/A substitution in exon 2, responsible for a genetically determined variation in splicing of the MUC1 transcript, has also been reported (Ligtenberg et al. 1990, 1991). Here we describe the detection of this nucleotide substitution polymorphism by single stranded conformational analysis of genomic DNA and we also report a CA repeat polymorphism within intron 6 of the gene. Haplotypes were determined in a series of families and the common alleles of these two polymorphisms were found to be associated. These results support the notion that the VNTR polymorphism in the coding sequence of MUC1 is not caused by unequal reciprocal recombination at meiosis.
Autosomal recessive disorders in Saguenay‐Lac‐Saint‐Jean (Quebec, Canada): a study of inbreeding
Authors: BRAEKELEER M. DE , GAUTHIER S. 
Published: September 2007

SummarySaguenay Lac‐Saint‐Jean (SLSJ) is a geographically isolated region of northeastern Quebec in which several autosomal recessive disorders have a high incidence. We calculated the inbreeding coefficients of 567 probands and compared them to 1701 matched control individuals. The mean inbreeding coefficient of the group containing all 567 probands was 2·73 times higher than that of the controls (0·001772 versus 0·00065). Thirteen percent (75/567) of the probands were inbred, but only 5% were born to matings between spouses related as second‐degree cousins or closer. No marriage between uncle and niece and only two marriages between first‐degree cousins were identified in the disorder group. These results strongly suggest that the high incidence of the autosomal recessive disorders in SLSJ is the result of a founder effect.
Isolation and mapping of three new polymorphic markers to chromosomes 3, 20 and 21
Authors: BOUZYK M. , EVANS C. , CULLIN L. , COX S. , WARNE D. , NYBERG K. , BRYANT S. P. , SPURR N. K. 
Published: September 2007

SummaryScreening of single human chromosome plasmid libraries using a digoxygenin labelled (AAAT)15 oligonucleotide probe led to the identification of several positive clones. DNA sequence analysis of these was carried out and showed the presence of a number of simple DNA repeats. Oligonucleotide primers were designed from the sequences flanking these repeats and tested in PCR amplification reactions of human genomic DNA. Three of the markers tested were shown to be polymorphic with heterozygosities ranging from 40% to 69%. The markers were assigned to chromosomes using a panel of monochromosomal somatic cell hybrids combined with linkage analysis using DNA from the CEPH panel of families. The markers designated (AAAT)11, (AAAT)12 and (CA)19 were thus assigned to chromosomes 3, 21 and 20 respectively.
Mitotic recombination among acrocentric chromosomes' short arms
Authors: GIUSSANI U. , FACCHINETTI B. , CASSINA G. , ZUFFARDI O. 
Published: September 2007

SummaryRoutine Q‐banding chromosome analysis detected the jumping behaviour of bright fluorescent chromosome 22 satellites (22s+) in two unrelated males (case 1 ascertained for recurrent abortions and case 2 for infertility), and in the mother of one of them, all with a normal karyotype. The 22s + was present in more than 90% of the cells. In a minority of the cells the polymorphism was present alternatively on another acrocentric, on one chromosome 22 and on another acrocentric, on both chromosomes 22 or it was absent. We take these findings as evidence of mitotic exchanges between the short arms of the acrocentric chromosomes. The presence of a stable 22s + in the fibroblasts of case 1 and in the lymphocytes of his son indicates that acrocentric short arm exchanges depend both on the type of tissue and on the genetic content of all the other acrocentrics.
A new intronic polymorphism in the C7 gene 36 bp from the common expressed C7 M/N polymorphism
Authors: FERNIE B. A. , WÜRZNER R. , ORREN A. , HOBART M. 
Published: September 2007

SummaryWe report a new polymorphism in the complement C7 gene that results from an A‐C transversion in intron 12, 27 bp upstream of exon 13 (C712.‐27) and 36 bp upstream of the point mutation that underlies the C7 M/N antigenic polymorphism. The C7 12.‐27 polymorphism subdivides C7 M haplotypes, but not C7 N. It also sheds light on the evolution of the various types of deficiency genes at the adjacent C6 locus.
Analysis of allelic structures at the D7S21 (MS31A) locus in the Japanese, using minisatellite variant repeat mapping by PCR (MVR‐PCR)
Authors: HUANG X‐L. , TAMAKI K. , YAMAMOTO T. , SUZUKI K. , NOZAWA H. , UCHIHI R. , KATSUMATA Y. , NEIL D. L. 
Published: September 2007

SummaryTo sample the diversity of allelic structures at the D7S21 (MS31A) locus in the Japanese, allele‐specific minisatellite variant repeat mapping using polymerase chain reaction (MVR‐PCR) was performed on genomic DNA from a number of Japanese individuals. Three polymorphic positions in the MS31A 5′ flanking DNA were typed from 214 un‐related Japanese, and the distribution of haplotypes was analysed. Allele‐specific MVR‐PCR, using primers that discriminate between different alleles at these polymorphic positions in heterozygous individuals, allows single alleles to be mapped from genomic DNA in approximately 80% of Japanese. 149 Japanese alleles have been mapped to date and all of them, except for two pairs of indistinguishable alleles, have different internal structures. More than half of the mapped alleles showed similar regions of internal structure to other alleles and were classified into groups on this basis.
The human complement C8G gene, a member of the lipocalin gene family: polymorphisms and mapping to chromosome 9q34.3
Authors: DEWALD G. , CICHON S. , BRYANT S. P. , HEMMER S. , NÖUTHEN M. M. , SPURR N. K. 
Published: September 2007

SummaryComplement component C8 is a plasma glycoprotein consisting of three nonidentical polypeptide chains (α, β, γ) which are encoded by three separate genes (C8A, C8B, C8G). The γ chain whose functional role remains undefined is not related to any other complement protein but is a member of the lipocalins, a family of proteins that bind small hydrophobic ligands. The present report describes the first known polymorphisms for the human C8G gene, namely one polymorphic site in exon 1 (207T/G) and two polymorphic sites in intron 1 (213 + 37G → A; 213 + 65del3). Specific typing can be performed using simple polymerase chain reaction‐based assays. C8G genotyping in eight CEPH reference families demonstrated that C8G is closely linked to a series of marker loci located in the most telomeric region of chromosome 9q. Multipoint analysis placed C8G with 1000:1 support distal to D9S207. C8G is thus located at 9q34.3. Remarkably, this chromosomal region contains at least four other lipocalin genes.
Multiple founder haplotypes of mitochondrial DNA in Amerindians revealed by RFLP and sequencing
Authors: SANTOS S. E. B. , RIBEIRO‐DOS‐SANTOS A. K. C. , MEYER D. , ZAGO M. A. 
Published: September 2007

SummaryThe mitochondrial DNA (mtDNA) of 139 individuals from eight tribes which belong to four linguistic groups of the Brazilian Amazon Region was studied both by RFLP and by sequencing of the D‐loop region. RFLP analysis showed that 41 haplotypes (29%) belonged to haplogroup A, 39 (28%) to haplogroup B, 38 (27%) to haplogroup C., 19 (14%) to haplogroup D, and 2 (<2%) could not be assigned to any of the four haplogroups. Among the 92 individuals analyzed by direct sequencing of the D‐loop region, we observed 43 different haplotypes defined by 48 polymorphic points, while one haplotype could not be assigned to any of the clusters previously described. Joint analysis of data obtained by RFLP and by sequencing of mtDNA demonstrated that, regardless of the method of analysis, the mtDNA haplotypes of contemporary Amerindians cluster into four groups, similar to those previously described, even though 7% of the total sample or 12% of the haplotypes have discrepancies between results obtained by RFLP and sequencing. In addition to supporting the prevalence of four major haplogroups among contemporary Amerindians, our data are compatible with multiple founder haplotypes in each haplogroup, based on: i) a high prevalence of unusual haplotypes; ii) presence of multiple polymorphic sites shared by different haplogroups; iii) relative differences in nucleotide diversity based on RFLP or sequencing within the different haplogroups.