bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional localization of the gene coding for the GM2 activator protein (GME2A) to chromosome 5q32‐33 and confirmation of the assignment of GM3AP to chromosome 3
Authors: SWALLOW D.M. , ISLAM I , FOX M. R. , POVERY S. , KLIMA H. , SCHEPERS U. , SANDHOFF K. 
Published: September 2007

SummaryThe gene coding for the GM2 activator protein (GM2A) was previously mapped by us to chromosome 5 by an ELISA‐based technique. Here we confirm this assignment using a PCR analysis of somatic cell hybrids and descrive a regional localization to chromosome 5q32‐33 by in situ hybridization. We also confirm the assignment of pseudogene GM2AP to chromosome 3.
Localization of the retinoid X receptor alpha gene (RXRA) to chromosome 9q34
Authors: JONES K. A. , FITZGIBBON J. , WOODWARD K. J. , GOUDIE D. , FERGUSON‐SMITH M. A. , POVEY S. , WOLFE J. , SOLOMON E. 
Published: September 2007

SummaryThe retinoid X receptor α is one of a number of retinoic acid receptors which are members of the steroid/thyroid hormone superfamily. Localization of RXRA was achieved using the polymerase chain reaction on a panel of somatic cell hybrids. A cosmid clone was isolated using the RXRA PCR product, and this was used to further localize the gene by fluorescence in situ hybridization to chromosome 9q34 distal to the dopamine β hydroxylase gene (DBH). This mapping position was confirmed by PCR on a panel of translocation hybrids.
Another procedure for the preliminary ordering of loci based on two point lod scores
Authors: CURTIS D. 
Published: September 2007

SUMMARYBecause of the difficulty of performing full likelihood analysis over multiple loci and the large numbers of possible orders, a number of methods have been proposed for quickly evaluating orders and, to a lesser extent, for generating good orders. A new method is proposed which uses a function which is moderately laborious to compute, the sum of lod scores between all pairs of loci. This function can be smoothly minimized by initially allowing the loci to be placed anywhere in space, and only subsequently constraining them to lie along a one‐dimensional map. Application of this approach to sample data suggests that it has promise and might usefully be combined with other methods when loci need to be ordered.
Disease susceptibility genes and the sib‐pair method: a review of recent methodology
Authors: SHAH S. , GREEN J. R. 
Published: September 2007

SUMMARYThere is now a considerable body of literature which describes and analyses various methods of testing for the presence of disease susceptibility genes by examining the degree of HLA haplotype sharing of parental haplotypes over random expectations amongst affected siblings. We here survey a number of improvements, generalizations and extensions of the earlier reported methods with the aim of bringing them to the attention of those who are collecting HLA or other haplotype data on familial disease.
Genomic cloning and localization by FISH and linkage analysis of the human gene encoding the primary subunit NMDAR1 (GRIN1) of the NMDA receptor channel
Authors: BRETT P. M. , BOURDELLES B. Le , SEE C. G. , WHITING P. J. , ATTWOOD J. , WOODWARD K. , ROBERTSON M. M. , KALSI G. , POVEY S. , GURLING H. M. D. 
Published: September 2007

SUMMARYA cDNA clone of the NMDAR1 (isoform E) has been used to screen both lambda and eosmid genomic libraries. A genomic phage clone was identified and sequenced and was found to contain some of the 3′ coding regions of the GRIN1 gene. This clone was used to localize the gene using fluorescent in situ hybridization (FISH) to normal chromosomes, and also to a lymphoblastoid cell line containing a translocation involving chromosomes 9 and 15. FISH localized the gene to chromosome 9q34.3. The clone was used to screen a panel of genomic DNAs cut with 20 restriction enzymes. A VNTR sequence 5′ to the gene, which was polymorphic for a number of restriction enzymes, was detected. A PvuII fragment of the genomic clone was found to detect the VNTR on Southern hybridization. The polymorphic VNTR marker was mapped against chromosome 9q34 markers using linkage analysis in the CEPH families. The GRIN1 gene was linked to D9S7 with a maximum lod score of 20·09 at zero recombination fraction in males and 0·03 % recombination in females.
Two loci for Tuberous Sclerosis: one on 9q34 and one on 16p13
Authors: POVEY S. , BURLEY M. W. , ATTWOOD J. , BENHAM F. , HUNT D. , JEREMIAH S. J. , FRANKLIN D. , GILLETT G. , MALAS S. , ROBSON E. B. , TIPPETT P. , EDWARDS J. H. , KWIATKOWSKI D. J. , SUPER M. , MUELLER R. , FRYER A. , CLARKE A. , WEBB D. , OSBORNE J. 
Published: September 2007

SUMMARY32 families informative for the segregation of Tuberous sclerosis (TSC) have been examined for genetic markers on chromosomes 9, 11, 12 and 16. In one large family there was clear evidence of linkage to markers on chromosome 16p13.3 (lodscore with D16S291 of 4·7 at θ= 0) but other families were too small to give individually convincing lodscores. Combined results for all families gave positive results with ABO/DBH on chromosome 9 (max lod 2·63) and with D16S291 on chromosome 16 (max lod 3·98) at values of theta of 0·2 in each case. Further analysis showed strong evidence for heterogeneity with approximately half the families linked to a locus TSC1 on chromosome 9 between ASS and D9S298 and half to TSC2 on chromosome 16 close to D16S291. There was no definite support for a third locus although in many families this could not be excluded. In three families the segregation pattern of TSC remains unexplained. In two of these the family apparently segregates for TSC1 but in each case a single affected individual appeared to exclude the whole of the candidate region. Preliminary analysis of clinical features did not reveal any definite differences in incidence of mental handicap between individuals in different linkage groups or with different sex of the parent of origin. The frequencies of periungual fibromas and facial angiofibromas were also similar in both linkage groups. The difficulties of detecting linkage in small families where there is locus heterogeneity are discussed. The program ZZ was found to be helpful in this respect.
Bootstrapping in human genetic linkage
Authors: CHIANO M. N. , YATES J. R. W. 
Published: September 2007

SUMMARYLinkage analysis of discrete Mendelian traits has made a major contribution to the mapping of the human genome. However, in more complex situations, particularly Mendelian disorders showing locus heterogeneity, linkage results have sometimes been misleading. The bootstrap confidence interval provides an assessment of the goodness of fit of the data to the genetic model and the presence of heterogeneity can inflate the confidence interval indicating that the fit is poor. The loss in statistical power and the potential unreliability of linkage analyses based on small samples or subsamples of pedigree material is explored and illustrated by using simulated data and also real data on 37 families affected by the heterogeneous disorder, tuberous sclerosis.
The distribution of Q: a powerful sibship test of association
Authors: SHAH S. , GREEN J. R. 
Published: September 2007

SUMMARYNon‐random inheritance of the two parental haplotypes among siblings affected by certain diseases has long been used to provide evidence of the presence of disease susceptibility genes. The distribution of a powerful test, called Q, based on haplotype concordance and discordance, is derived under the null hypothesis of random inheritance of haplotypes by affected siblings. The presence of a disease gene possibly linked to one of the haplotypes causes a change in the distribution of these haplotypes in the affected siblings. This distribution is found to be that of the sum of two independent variates contributed by the two parents in all parental types except one where both parents are heterozygous for the disease allele; which is dealt with separately. For comparison, the tables showing the powers of the test along with those of another well‐known test, the N‐test of haplotype concordance, are given. This is because Q is a modification of N to deal with the case when information on unaffected siblings is also available.
DNA polymorphisms of the complement C6 and C7 genes
Authors: FERNIE B. A. , WÜRZNER R. , UNSWORTH D. J. , TUXWORTH R. I. , HOBART M. J. 
Published: September 2007

SUMMARYThe linked C6 and C7 loci are rich in genetic markers, both at the protein and DNA levels. There are now seven common DNA polymorphisms distributed over about 300 kbp of chromosome 5p12‐14. We report a new TaqI RFLP for C7 and a method for typing a C7 variant (T368S) hitherto known only from cDNA clones. We have re‐investigated the published RFLPs to provide information on their frequency in North European Caucasian (predominantly British and Irish) subjects and have revised some of the published parameters, especially the sizes of polymorphic restriction fragments. Their precise locations within the genes are also reported: the three markers for C6 are in exon 3, intron 3 and adjacent to exon 17 and the four markers for C7 are in introns 15 and 13 and in exons 13 and 9. The gene frequencies of the second commonest allele of all seven markers lie in the range 0·2 to 0·37, except C6 A/B in the Japanese, where the frequencies of both common alleles are about 0·45. We have estimated the gene frequencies for the DNA polymorphisms which correlate with C7 M/N phenotype and for the C6 A/B phenotype and find them to be the same as the phenotypic estimates in Caucasians and in the Japanese respectively. The markers provide the possibility of defining 128 haplotypes, many (28) of which have been observed. Allelic associations in these genes are generally surprisingly weak.
Complement component C6 and C7 haplotypes associated with deficiencies of C6
Authors: FERNIE B. A. , ORREN A. , WÜRZNER R. , JONES A. M. , POTTER P. C. , LACHMANN P. J. , HOBART M. J. 
Published: September 2007

SUMMARYBoth complete C6‐deficiency (C6*Q0) and subtotal C6‐deficiency (C6*SD) have been described as simple recessive traits and C6*SD has been described in combination with subtotal deficiency of the C7 coded at an adjacent locus. The trace of C6 protein found in both C6*SD traits is phenotypically indistinguishable, being smaller than normal C6 and having different isoelectric properties. A defect has been found in the C6 gene which plausibly explains the C6*SD phenotype, and this defect is also common to both C6*SD traits. We present data from seven DNA markers of the C6 and C7 genes which show that although at least four haplotypes are associated with C6*Q0, most South African C6*Q0 patients carry a common defective haplotype. The most common haplotype associated with C6*Q0 has been observed only once among unaffected haplotypes of relatives. In one family, the cases of C6*SD share a complete haplotype with both cases of combined deficiency and are probably heterozygous for this condition and complete deficiency of C6. In another family, the C6*SD is on a slightly different haplotype and C7 is normally expressed. Thus, the C6 defect is not sufficient on its own to explain the C7 deficiency in the combined deficient haplotype. The haplotype associated with the combined deficiency is found not only in normal control subjects, but also in one case of complete C6 deficiency. In this case the molecular defect seen in combined or C6*SD cases is absent.
Apolipoprotein E polymorphism in Italy investigated in native plasma by a simple polyacrylamide gel isoelectric focusing technique. Comparison with frequency data of other European populations
Authors: CORBO R. M. , SCACCHI R. , MUREDDU L. , MULAS G. , ALFANO G. 
Published: September 2007

A new polyacrylamide gel isoelectric focusing (PAGIEF) technique has been developed that allows rapid and reliable identification of Apolipoprotein E (APOE) phenotypes directly from plasma or serum without any prior treatment.This method was used to determine the APOE phenotypes in samples from Central and Southern Italy, Sicily, and Sardinia. The frequencies observed for the APOE*2, APOE*3, and AP0E*4 alleles in Central and Southern Italy (Sicily included) were similar (0·066, 0·851, 0·083 and 0·056, 0·858, 0·085 respectively) though lower APOE*4 frequencies were found in the more southern regions. The Sardinian population showed APOE gene frequencies (APOE*2= 0·050, APOE*3= 0·898, AP0E*4= 0·052) to be significantly different from those of the rest of Italy owing to the low AP0E*4 frequency, the lowest among Caucasian populations. The frequencies were compared with those found in other European populations. A clear cut North‐South decreasing cline was found for APOE*4 allele frequencies and an opposite trend was found for AP0E*3 frequencies. The overall dispersion of European populations as determined by the three APOE allele frequencies was graphically represented using coordinate analysis. The tendency of the APOE*4 frequency to decline with latitude both at the Italian and at the European level was discussed with reference to similar trends observed for dietary habits (saturated fat intake).
What stabilizes the sex ratio?
Authors: JAMES W. H. 
Published: September 2007

SUMMARYIt is suggested that the human sex ratio at birth is stabilized only to a minor extent by the direct processes of natural selection. Instead the major factors stabilizing sex ratio seem to be behavioural (coital rates) and psychological (parental perceptions of adult sex ratios). It is suggested that parental hormone levels are (a) a consequence of perceived adult sex ratios, and (b) a cause of sex ratio in the next generation, thus providing the basis for a negative feedback process stabilizing the sex ratio.
Structure of the human deoxyribonuclease I (DNase I) gene: identification of the nucleotide substitution that generates its classical genetic polymorphism
Authors: YASUDA T. , KISHI K. , YANAGAWA Y. , YOSHIDA A. 
Published: September 2007

SummaryThe objectives of this study were to elucidate the structural organization of the gene for human deoxyribonuclease I (DNase I) and to identify the mutation site underlying its classical genetic polymorphism. In order to determine the organization of this gene, we utilized a combination of direct polymerase chain reaction (PCR)‐amplification of human genomic DNA and isolation of the overlapping clones from a cosmid human genomic library. Restriction endonuclease mapping, Southern blotting and DNA sequencing showed that the DNase I gene was approximately 3·2 kilobases long, it comprised 9 (I‐IX) exons separated by eight introns and its complete sequence was determined. The first exon contained only the non‐translated sequences of mRNA. In addition to several putative regulatory elements, TATA‐like and CAAT‐like sequences were observed in the region upstream of the translation initiation codon. These results provide information that will help to understand the expression and regulation of DNase I. The isoelectric focusing patterns of human DNase I showed that it exhibits classical genetic polymorphism (Kishi et al. 1989, 1990). A comparison of the entire translated sequences of the DNase I gene from two pairs of individuals with common DNase I phenotypes 1 and 2 revealed only one nucleotide residue difference in exon VIII, A for phenotype 1 and G for phenotype 2, thus producing Gin and Arg amino acid substitutions respectively at position 222 from the NH2‐terminus of the mature enzyme. The predicted charge changes attributable to these amino acid substitutions are entirely consistent with the isoelectric focusing profiles of these two DNase I isozymes. We conclude that this substitution is solely responsible for the classical polymorphism of DNase I protein.
Posterior probability of linkage and maximal lod score
Authors: GÉNIN E. , MARTINEZ M. , CLERGET‐DARPOUX F. 
Published: September 2007

SummaryTo detect linkage between a trait and a marker, Morton (1955) proposed to calculate the lod score z(θ1) at a given value θ1 of the recombination fraction. If z(θ1) reaches +3 then linkage is concluded. However, in practice, lod scores are calculated for different values of the recombination fraction between 0 and 0·5 and the test is based on the maximum value of the lod score Zmax. The impact of this deviation of the test on the probability that in fact linkage does not exist, when linkage was concluded, is documented here. This posterior probability of no linkage can be derived by using Bayes' theorem. It is less than 5% when the lod score at a predetermined θ1 is used for the test. But, for a Zmax of +3, we showed that it can reach 16·4%. Thus, considering a composite alternative hypothesis instead of a single one decreases the reliability of the test. The reliability decreases rapidly when Zmax is less than + 3. Given a Zmax of +2·5, there is a 33% chance that linkage does not exist. Moreover, the posterior probability depends not only on the value of Zmax but also jointly on the family structures and on the genetic model. For a given Zmax, the chance that linkage exists may then vary.
Characterisation of a human chromosome 1 somatic cell hybrid mapping panel and regional assignment of 6 novel STS
Authors: ROBERTS T. , MEAD R. S. , COWELL J. K. 
Published: September 2007

SUMMARYA somatic cell hybrid mapping panel has been constructed which allows subdivision of human chromosome 1 into 8 distinct subregions. All of the hybrids carry copies of chromosome 1 with specific deletions and the position of the breakpoints has been determined relative to the location of microsatellite markers in the genetic linkage map produced by Genethon. The majority of the breakpoints can be positioned between adjacent loci on the map. The usefulness of this hybrid panel for physical mapping has been demonstrated by the regional assignment of 6 novel STS markers made from Alu‐PCR clones generated from a hybrid which contains the short arm of chromosome 1.
Variants at the secretory phospholipase A2 (PLA2G2A) locus: analysis of associations with familial adenomatous polyposis and sporadic colorectal tumours
Authors: TOMLINSON I. P. M. , BECK N. E. , NEALE K. , BODMER W. F. 
Published: September 2007

SUMMARYThe Min mouse is a model for human familial adenomatous polyposis (FAP), an autosomal dominant disease characterised by multiple adenomatous gastrointestinal polyps. The severity of the Min phenotype is modified by a locus (Mom1) on mouse chromosome 4, at a position syntenic with human chromosome 1p35‐p36. The secretory phospholipase A2 (Pla2s) gene is a candidate for this modifier locus and there is evidence that a locus on human chromosome 1p35‐p36 acts to modify the severity of human duodenal FAP. We have analysed the human secretory phospholipase A2 locus (PLA2G2A) for variants that could directly influence the FAP phenotype. We found no PLA2G2A variants predicted to result in functional variation in the phospholipase A2 protein. Two PLA2G2A polymorphisms were, however, discovered, one a ‘silent’ base change in exon 3 and another in a non‐coding region. Three other variants (possible mutations) were found in non‐coding regions. In 70 FAP patients from 20 families, no associations were found between the severity of duodenal polyposis and any PLA2G2A variant. One allele at the exon 3 polymorphic site did, however, occur more often then expected in patients with relatively severe colonie FAP. Although of borderline statistical significance, this association, if genuine, is likely to result from linkage disequilibrium between the PLA2G2A alleles studied and undetected genetic variation at a closely linked locus. The frequency of the alleles at both polymorphic sites has also been determined in the germ line of patients with sporadic colorectal adenomas and carcinomas and in random controls, but no differences were found among these groups. Our results suggest that PLA2G2A variants do not influence inherited or sporadic colonie tumours. A linked locus may be a modifier of human FAP, but does not influence the risk of colorectal tumours in the general population.
Human sequences homologous to the gene for the cochlear protein Ocp‐II do not map to currently known non‐syndromic hearing loss loci
Authors: BROWN K. A. , LEEK J. P. , LENCH N. J. , MOYNIHAN L. M. , MARKHAM A. F. , MUELLER R. F. 
Published: September 2007

SUMMARYThe abundant and almost exclusive expression of OCP‐II protein in the mammalian cochlea has fuelled speculation that mutations in the OCP2 gene may result in inherited forms of hearing impairment. We have identified several human sequences related to OCP2 and sublocalised three of these OCP2 related loci to 4q12‐p14 or 4p16.2‐pter, 5q15‐q21.3 and 7p22‐q22 by PCR. 2 YACs with sequence consistent with the chromosome 7 locus were also used for FISH analysis and hybridised to chromosome 7q11. Our data suggest that the cytogenetic localisations of these OCP2 related sequences do not correlate with the precise chromosomal positions of deafness loci so far identified.
Geographic clustering of human Y‐chromosome haplotypes
Authors: LINARES A. RUIZ , NAYAR K. , GOLDSTEIN D. B. , HEBERT J. M. , SEIELSTAD M. T. , UNDERHILL P. A. , LIN A. A. , FELDMAN M. W. , SFORZA L. L. CAVALLI 
Published: September 2007

SUMMARYFive polymorphic markers on the Y‐chromosome (mostly microsatellites) were typed in 121 individuals from 13 populations around the world. With these markers 78 different haplotypes were detected. Haplotypes present more than once tend to be shared by individuals from the same population or continent. A reconstruction of haplotype phylogeny also indicates significant geographic structure in the data. Based on the similarity of the haplotypes, population relationships were examined and found to be largely concordant with those obtained with other markers. Even though the sample size and the number of markers are small, there is very signficant clustering of the haplotypes by continent of origin.
Ancestry and interrelationships of the Indians and their relationship with other world populations: A study based on mitochondrial DNA polymorphisms*
Authors: BARNABAS S. , APTE R. V. , SURESH C. G. 
Published: September 2007

SUMMARYMitochondrial DNA variation was studied in 100 Indians using the same set of six restriction enzymes used in the study of other world ethnic groups in order to compare and discern possible relationships of the Indian populations. Twenty nine mtDNA types were found including the ones from an earlier study (Semino et al. 1991) and unweighted pair‐group method (UPGMA) and maximum parsimony trees were constructed using the mtDNA types. The nucleotide diversity values were calculated using the maximum likelihood method. From a study of the shared mitochondrial DNA types and the parsimony tree (Fig. 2) we came to the conclusion that the Indian population is closer to Caucasians and has an admixture with Asians. The North Indian population appears to have a recent admixture of the Caucasian mtDNA types which is absent in the south.