bluuebunny/crossref_metadata_2025_split huggingface dataset:
The human chromosome 19 linkage group FUT1 (H), FUT2 (SE), LE, LU, PEPD, C3, APOC2, D19S7 and D19S9
Authors: BALL S. P. , TONGUE N. , GIBAUD A. , PENDU J. LE , MOLLICONE R. , GERARD G. , ORIOL R. 
Published: September 2007

SUMMARYFamilies segregating for deficiency of the H α‐2‐L‐fucosyltransferase, FUT1, have been investigated for linkage between FUT1 and other markers on chromosome 19. The results provide evidence for close linkage between FUT1 and FUT2 and for looser linkage between FUT1 and APOG2 and between FUT1 and D19S7. Pairwise linkage data are also reported between other markers investigated.
Population genetics of vitamin D‐dependent rickets in northeastern Quebec
Authors: Braekeleer M. De , Larochelle J. 
Published: September 2007

SummaryVitamin D‐dependent rickets (VDD1) is an autosomal recessive disorder that was recognized in Saguenay‐Lac‐St‐Jean (SLSJ) in 1970. The great majority of the VDDl cases reportedin the French Canadian population of Quebec originated from SLSJ, Charlevoix, and the Haute CGte Nord, all regions located in northeastern Quebec. The prevalence a t birth in SLSJ was estimated a t 112916 live borns, and the carrier rate was estimated a t 1/27 inhabitants in the SLSJ region. The mean coefficient of inbreeding was not elevated in the VDDlgroup of SLSJ compared with three matched control groups. The mean coefficient of kinshipwas 2.5 times higher in the VDDl group than in the control groups. In the SLSJ region, the places of origin of the VDDl children and their children did not show a clustered non‐uniform distribution. Endogamy was not found to be higher in the VDDl group than in controlgroups. The genealogical reconstruction showed all the obligate carriers of the VDDl gene, but one, to be related to a small set of founders who settled in New France in the 17thcentury. All these results, as well as a strong linkage disequilibrium between RFLPs located on the long arm of chromosome 12 and the VDDl locus, support the hypothesis of a founder effect for VDDl. They also suggest that a unique mutation accounts for most, if not all, of the cases known in northeastern Quebec.
Using a dummy quantitative variable to deal with multiple affection categories in genetic linkage analysis
Authors: Curtis D. , Gurling H. M. D. 
Published: September 2007

SummarySome diseases which have a genetic contribution to aetiology do not demonstrate a clear correspondence between genotype and phenotype. A variety of different clinical syndromes may be thought to reflect the action of a gene, but the probability of affection conditional on genotype may vary between these different diagnostic categories. The normal approach of repeating linkage analyses several times using different diagnoses to define individuals as affected loses power in two ways: multiple testing must be allowed for, and the distinction between more and less extreme forms of affection is lost. It is shown that for fully dominant or recessive autosomal diseases it is straightforward to assign a quantitative value to each diagnostic category to obtain the desired ratio of the likelihoodsof affection conditional on the three possible genotypes. The increased power provided byusing this quantitative value in linkage analysis is demonstrated by application to simulated pedigrees containing cases of bipolar and unipolar affective disorder.
The number of loci needed for ELOD calculations
Authors: LEWIS C. M. , CANNINGS C. 
Published: September 2007

SummaryThis theoretical approach to multiple markers considers the problem of a trait locus flanked by an arbitrary number of linked, ordered markers. Using the criterion of the Expected LOD score (ELOD) for mating, an algorithm is developed to specify the subset of markers required to provide the full linkage information available from a given parental genotype.
Strategies based on marker information for the study of human diseases
Authors: CLERGET‐DARPOUX F. , BONAÏTI‐PELLIÉ C. 
Published: September 2007

SummaryThe goals and the ways of using genetic marker information when studying human disease are very different according to whether the disease or sub‐entity of the disease is mendelian or if a ‘disease gene’ in the sense of a rare mutated allele does not exist but rather common genetic risk factors, each one normal if considered alone. In the former case, genetic markers are used in the aim of localizing the defective gene and a systematic screening of the genome seems to be an efficient strategy provided there is not too much ambiguity in the correspondence between phenotypes and genotypes. In the latter case, the goal is to find risk factors allowing us to predict better the risk for an individual and to define different risk groups resulting in greater power to show the potential role of other factors (genetic or environmental). In this situation, the use of the lod score method with random markers presents several disadvantages: first, the multiple testing problem is particularly crucial; second, false rejection of linkage may be induced by misspecification of the model describing the genetic basis of the disease; and last, the power of detecting linkage may be low. A strategy focusing on ‘candidate gene’ markers may be then more efficient.
The AD1 locus in familial Alzheimer disease
Authors: LAWRENCE S. , KEATS B. J. , MORTON N. E. 
Published: September 2007

SummaryThe AD1 locus on chromosome 21 (MIM 104300) maps to the β‐amyloid precursor locus (APP) at approximately 27·7 Mb from pter (10·9 cM in males and 33·9 cM in females), flanked proximally by D21S8 and distally by D21S111, with D21S124 and D21S210 close but of uncertain order. AD1 accounts for 63±11 % of multiplex Alzheimer pedigrees for which lod scores have been reported. Since a much smaller proportion of pedigrees have mutations in the cDNA for β‐amyloid (APP exons 16 and 17), it is likely that the AD1 locus spans controlling elements near those exons. There is no evidence for a second locus on chromosome 21. The remaining pedigrees may include sporadic cases as well as mutations at an AD2 locus on another chromosome.
A Y‐associated allele may be characteristic of certain ethnic groups in Asia
Authors: NAKAGOME Y. , YOUNG S. R. , AKANE A. , NUMABE H. , JIN D. K. , YAMORI Y. , SEKI S. , TAMURA T. , NAGAFUCHI S. , SHIONO H. , NAKAHORI Y. 
Published: September 2007

SummaryThe probe 47z detects DNA polymorphisms on both the X and Y chromosomes. Blood samples were collected from Korean, Chinese, Jewish, Caucasian and Negro populations and polymorphisms of both loci were compared with findings previously reported in Japanese. Both Y1 and Y2 alleles were detected in Japanese and Koreans. However, only the Y1 allele was detected in each of the other populations. Although, both X1 and X2 alleles were detected in all examined populations, the frequency of the X2 allele was very low among Negroes.
Human regeneration protein/lothostathine genes map to chromosome 2p 12
Authors: Gharib B. , Fox M.F. , Bartoli C. , Giorgi D. , Sansonetti A. , Swallow D. M. , Dargorn J. C. , Berge‐Lefrance J. L. 
Published: September 2007

SummaryThe pancreatic stone protein (lithostathine) secreted by the exocrine pancreas is an inhibitor of CaCO3 crystal growth. This protein, which is also present in endocrine pancreas, has also been called the regeneration protein (reg). Here we report the mapping of the REG gene to chromosome 2 using the polymerase chain reaction for the specific amplification of human reg sequences in rodentlhuman somatic cell hybrid DNA. A regional assignment has been made by in situ hybridization to metaphase chromosomes using two different fluorescently labelled genomic probes corresponding to the REG gene and a related gene REGL. Both probes hybridized to chromosome 2p12 suggesting the tandem organization of these genes.
Optical density profile analysis of trypsin‐Giemsa bands in human X‐chromosomes
Authors: PÁSARO E. , FERNÁNDEZ R. , MÉNDEZ J. 
Published: September 2007

SummaryMean Optical Density (M.O.D.) determination of six G‐bands on X‐chromosomes was performed on 45 patients with Turner's syndrome and cjompared with X‐chromosomes from women controls with a normal karyotype by a Chromosome Image Analysis System. Density profiles were constructed to obtain standard values for the staining intensity and frequency of occurrence of chromosome bands. Statistical analysis showed that the M.O.D. were significantly different for Xq12, Xq21, Xq25 and Xq27 G‐bands between the Turner and Control groups. Most within‐group differences were small and appeared not to be statistically significant.
Estimation of the intraclass correlation coefficient
Authors: SRIVASTAVA M. S. 
Published: September 2007

SummaryWhen families have different numbers of offspring, the maximum likelihood procedure for estimating the intraclass correlation is iterative, requiring considerable computation. Occasionally, the iterations do not even converge. To overcome this difficulty, several noniterative estimators have been proposed by Smith (1956). However, to choose from among these estimators, some prior knowledge of the intraclass correlation is needed. In this paper, a combination estimator is proposed. The asymptotic variance of this estimator is given and compared with those of the two most commonly used estimators. The comparison shows that the combination estimator always performs better than the uniform weight estimator and the loss in efficiency is not more than 7% when it is used in place of Fisher's estimator.
Identification and regional localization of a highly polymorphic dinucleotide repeat D11S614 to the interval in 11q23.3 flanked by recurrent translocation breakpoints
Authors: BENHAM F. , SUGIYAMA R. , HUNT D. , GILLETT G. , SMITH M. 
Published: September 2007

SummaryA higly informative dinucleotide repeat polymorphism has been identified at the D11S614 locus on chromosome 11q23. Ten differen alleles have been observed at this locus, and the heterozygosity frequency is approximately 85%. Physical localization of this marker in a panel of somatic cell hybrids containing chromosome 11 translocation showed that is maps to 11q23.3, within the interval between the recurrent t(4;11) leukaemia breakpoint and the t(11;22) Ewing's sarcoma breakpoint. This physical mapping data is consistent withs the genetic mapping which indicates tight linkage to other markers in the q23.3 region including PBGD, CD3D and D11S29. Regional localization of highly informative markers such as D11S614 will facilitate integration of the genetic and physical maps.
Localization of the Tamm‐Horsfall glycoprotein (unomodulin) gene to chromosome 16p12.3‐16p13.11
Authors: POOK M. A. , JEREMIAH S. , SCHEINMAN S. J. , POVEY S. , THAKKER R. V. 
Published: September 2007

SummaryMapping studies using a panel of 22 rodent‐human somatic cell hybrids have helped to localize the Tamm‐Horsfall glycoprotein (uromodulin) gene (UMOD): which has previously been reported to map to 16p13.11, to the region 16p12.3‐qter. The combined results indicate that UMOD is located distal to D16S295 and proximal to D16S287 and in the region 16p12.3‐16p13.11. Uromodulin is known to affect the formation of calcium‐containing kidney stones, and this localization of UMOD will help in studies of families with autosomal forms of nephrolithiasis.
Regional localization of the lactase‐phlorizin hydrolase gene, LCT, to chromosome 2q21
Authors: HARVEY C. B. , FOX M. F. , JEGGO P. A. , MANTEI N. , POVEY S. , SWALLOW D. M. 
Published: September 2007

SummaryThe gene LCT which codes for the intestinal disaccharidase lactase‐phlorizin hydrolase has previously been mapped, using somatic cell hybrids and linkage analysis, using the CEPH families, to chromosome 2. We describe here the regional localization of LCT to chromosome 2q21 by polymerase chain reaction (PCR) analysis of somatic cell hybrids and in situ hybridization. LCT is closely linked to D2844, with a lod score of 30.6 at θ= 0.10.
Testing for haplotype concordance with incomplete parental data ‐ modified Q and correction for modified N
Authors: SHAH S. , GREEN J. R. 
Published: September 2007

SummarySome errors have been found in the distribution of modified N in a paper by Green & Grennan (1991). These have now been corrected, also a modified form of a new test ‐ criterion Q is presented. Both are applied to data.
‘SZ like’α1‐antitrypsin phenotypes in PI ZZ children with liver disease
Authors: WHITEHOUSE D. B. , LOVEGROVE J. U. , MIELI‐VERGANI G. , MOWAT A. P. , HOPKINSON D. A. 
Published: September 2007

SUMMARYUsing high resolution isoelectric focusing, α1‐antitrypsin phenotypes were studied in 106 individuals of the PI ZZ genotype including 71 with liver disease, 22 with chest disease and 13 healthy subjects. The resulting Z patterns were found to be highly variable. In the majority of cases (89/106) the maximum staining intensity was either in the most basic isoform or shared equally between two basic isoforms of the Z phenotype. However, in 17 cases there was a marked intensification of the more acidic isoforms resulting in a pattern which closely resembled the SZ phenotype. This ‘SZ like’ pattern occurred more frequently in the liver group (16/71) than the chest group (0/22) or healthy (1/13) controls. One possible consequence of the ‘SZ like’ pattern is confusion with the genuine SZ phenotype leading to misclassification. If this were so, there could be an erroneous exaggeration of the actual incidence of childhood liver disease associated with PI SZ.
Evaluation of a transgenic mouse model for alpha‐1‐antitrypsin (AAT) related liver disease
Authors: ALI R. , PERFUMO S. , ROCCA C. della , AMICONE L. , POZZI L. , McCULLAGH P. , MILLWARD‐SADLER H. , EDWARDS Y. , POVEY S. , TRIPODI M. 
Published: September 2007

SUMMARYWe have attempted to produce a transgenic mouse model of the neonatal liver disease associated with the human PIZ allele. Analysis of a number of transgenic mouse lines carrying either a normal human PIM gene construct or the mutant Z is reported. Using isoelectric focusing analysis of plasma from transgenic mice, we have shown that the human AAT proteins produced in mice are processed in a similar way to their counterparts in humans. By comparing the level of M and Z mRNA in liver with the levels of M and Z proteins in plasma we have inferred that, as in humans, the mutant protein tends to accumulate within the hepatocyte. Accumulation of Z protein has also been demonstrated by immunocytochemistry. Two of the M transgenic lines produce such high levels of the human protein that it, like the Z protein, accumulates as globules. Histological features of livers from 116 mice of different ages and genotypes were examined: 37 non‐transgenic, 62 Z transgenic (23 low expressing and 39 high expressing) and 17 M transgenic mice, all high expressing. Cirrhosis or fibrosis was not seen in any animal and we were unable to find any evidence for neonatal liver disease. Some necrosis was seen in all genotypes and this increased significantly with age with one Z line showing significantly more frequent necrosis than any other group. This line, the highest expressing Z line, was back crossed onto 7 different genetic backgrounds but no major differences between the back crosses with respect to liver disease were observed. The mouse model we have developed is compared with other transgenic Z mouse models; none of these is representative of human neonatal liver disease. Our view is that the transgenic animals generated in these experiments may be most useful for investigating the liver manifestations that almost invariably occur in ZZ adults. Alteration of additional factors other than accumulation of Z protein, for example inactivation of the endogenous mouse genes or some environmental challenge, might produce a mouse model with more relevance to neonatal liver disease.
Age of onset in familial adenomatous polyposis: heterogeneity within families and among APC mutations
Authors: PRESCIUTTINI S. , VARESCO L. , SALA P. , GISMONDI V. , ROSSETTI C. , BAFICO A. , FERRARA G. B. , BERTARIO L. 
Published: September 2007

SUMMARYHeterogeneity among and within FAP pedigrees for the age of symptom onset and the age at death from colorectal cancer was studied in a sample of 583 patients of the Italian Polyposis Registry. The among pedigree variation was largely explained by clustering of families in two groups, ‘early FAP’ (most colorectal cancer deaths below 45 years of age) and ‘late FAP’ families (most deaths above age 45). The within‐family variation was explained by a marked phenomenon of anticipation (15 years per generation, on the average), possibly not due to ascertainment bias. We then considered the pedigrees with identified mutation in the APC gene. Six families shared a common deletion at codon 1309 and showed the early FAP phenotype. Two families shared a mutation at codon 1061 and revealed the late FAP phenotype. Another two families (codons 453 and 302) clustered with the late FAP group, whereas a family with mutation at codon 835 clustered with the early FAP group. We suggest that there are at least two classes of mutations in the APC gene with different consequences at the phenotypic level. It seems that there are several critical points within the APC protein sequence at which truncation causes a more aggressive disease than truncation at other points.
An algorithm for Monte Carlo estimation of genotype probabilities on complex pedigrees
Authors: LIN S. , THOMPSON E. , WIJSMAN E. 
Published: September 2007

SUMMARYExact probability and likelihood computation on complex pedigrees is often infeasible, since exact methods are too computationally intensive even with today's computing technology. A statistical tool, Markov chain Monte Carlo (MCMC), is increasingly being explored as a technique for estimating probabilities of genotypic configurations on pedigrees conditional on phenotypic data. However, this conditional probability distribution on a complex pedigree is, in general, multimodal, and multimodality is one of the major difficulties in MCMC exploration of a probability surface. In this paper, a new member of the MCMC Metropolis‐Hastings class of algorithms is proposed; the heated‐Metropolis algorithm. The algorithm achieves passage through low probability states to other local modes of the probability distribution, and so provides much improved estimates of probabilities of interest. The example considered is the estimation of the probabilities of carrier genotype for the founders of a complex pedigree in which a very rare lethal recessive trait is segregating.
Genetic and environmental effects on coronary heart disease risk factors in Northern Norway. The cardiovascular disease study in Finnmark
Authors: BRENN T. 
Published: September 2007

SUMMARYThis study comprised 1377 first degree relatives in 575 families ascertained through a comprehensive screening of the general population from 20 to 52 years of age. Path analysis using parsimonious models gave evidence of significant biologic and environmental transmission for total cholesterol (genetic and cultural heritabilities were 0·46 and 0·05, respectively), high density lipoprotein cholesterol (0·42, 0·10), triglycerides (0·21, 0·07), and systolic (0·48, 0·04) and diastolic (0·35, 0·05) blood pressure. Compared with other studies employing the same path analytic model, heritability estimates in general were among the highest reported, except for the somewhat lower genetic component in total cholesterol and triglycerides. For the first time in a single sample from the general population, lipid and blood pressure variables were investigated applying the same methodology, and good agreement was illustrated by the result that identical parsimonious models were reached for all phenotypes, with the exception of a single additional parameter for total cholesterol. About one fourth to one half of the total phenotypic variance could be ascribed to genetic sources, whereas the contribution from shared familial environment was much smaller.
A note on testing the Hardy‐Weinberg law across strata
Authors: TROENDLE J. F. , YU K. F. 
Published: September 2007

SUMMARYThe problem of testing the Hardy‐Weinberg law when the data are stratified in K strata is considered. Previous methods lose power when the departure from the law is irregular from stratum to stratum. Two methods based on the squared distance are proposed to overcome this problem. Simulations show that the new methods can have a dramatic improvement over the previous methods. The methods are applied to red cell glyoxalase genotype data from populations in India.
The genetic affinity of Polynesians: evidence from Y chromosome polymorphisms
Authors: SPURDLE A. B. , WOODFIELD D. G. , HAMMER M. F. , JENKINS T. 
Published: September 2007

SUMMARYY‐linked polymorphisms were studied in a sample of 60 Polynesians, and results were compared with findings from studies on other major population groups. Three previously unreported 49a/TaqI haplotypes were observed, two of which possess a new polymorphic fragment named 12. Frequency data for the 49a/TaqI, XY275, pDP31 and Y Alu polymorphisms indicate that Polynesians have greater affinity to Caucasoids than to African populations. Similar population frequency trends were not observed for the p21A1/TaqI polymorphism, supporting the hypothesis that this polymorphism has arisen more than once.
Molecular variation of the human elastin (ELN) gene in a normal human population
Authors: RAYBOULD M. C. , BIRLEY A. J. , HULTÉN M. 
Published: September 2007

SUMMARYDNA sequence diversity in the human elastin genomic region has been estimated by RFLP analysis in a normal human population. The proportion of polymorphic nucleotides and the degree of nucleotide diversity were 0·0034 and 0·0018 respectively. It is argued that the estimate of nucleotide diversity does not indicate strong purifying selection in the region. A total of 144 restriction sites were sampled in each of 80 independent chromosomes representing the screening of 58080 bp overall. Six main haplotypes were constructed; they represent at least 84% of the 80 chromosomes sampled. Analysis for linkage disequilibrium revealed two statistically significant comparisons out of 54 tests, approximately the proportion that would be statistically significant at the 5% level by chance. A higher order quadrigenic disequilibrium was detected. The relationship between the physical distance separating polymorphic restriction sites and linkage disequilibrium is discussed. The development of elastin haplotypes and knowledge of the pattern of linkage disequilibrium should aid the study of elastin related disease and human evolution.
Genetic epidemiology of breast cancer: interest of survival analysis methods
Authors: ESSIOUX L. , ABEL L. , BONAIÏTI‐PELLIÉ C. 
Published: September 2007

SUMMARYIn an attempt to explain the controversy resulting from the analysis of the breast cancer data collected by Jacobsen, a segregation analysis was performed using successively the unified mixed model (UM) and the logistic hazard function model (LHM) (Abel & Bonney, 1990). Under the UM, age of onset of the disease cannot be taken into account, each individual being assigned to a liability class according to his age at examination, whereas, in the LHM, variable age of onset is modelled using survival analysis methods.Under the UM, we confirmed the results of Demenais et al. (1986b), i.e. the transmission probabilities are significantly different from Mendelian expectations. The same results were obtained when taking into account the specific mortality for the computation of the morbid risk observed in a given liability class. Lender the LHM, the analysis provides evidence for a monogenic autosomal model with a rare dominant allele responsible for the disease, and transmission probabilities compatible with Mendelian expectations.