bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the origins of human trisomies and triploids
Authors: THOMSON R. 
Published: September 2007

8. SUMMARYA counting method has been developed to estimate the probabilities of origin of trisomy and triploidy. A method for finding the standard errors of the estimators has also been developed. It has also been shown that this counting method is equivalent to the method of maximum likelihood. The method extends to situations representable by ‘tree diagrams’.
Statistical methods for assessing linkage disequilibrium at the HLA‐A, B, C loci
Authors: KARLIN S. , PIAZZA A. 
Published: September 2007

SUMMARYA number of standard and new statistics for measuring linkage disequilibrium are introduced applicable to any multilocus system. Included are the usual pairwise gametic disequilibrium function, D, the Lewontin disequilibrium index, DL, a Euclidean disequilibrium distance, DE, a hierarchy of stratified linkage disequilibrium functions (e.g. a pairwise disequilibrium value conditioned on the value of a third locus) and an averaged conditional disequilibrium expression, DW. Various global second order measures of disequilibrium are proposed partly based on contingency table statistics and weighted pairwise disequilibrium quantities. A non‐parametric (stochastic) comparison assessment for global linkage disequilibrium is also developed. These measures are compared and contrasted at the HLA‐A, B, C gene complex for a sample of 2000 haplotypes from a healthy Austrian population.Several results from applying these methods include: (1) Of the various pairwise disequilibrium measures examined, D, DE and DW correlated very closely with each other but differ from DL. (2) The ‘third‐order interaction’ between two loci conditional on an allele (or group of alleles) at a third locus indicated that HLA‐AB maintains the classical disequilibrium pairings only for conditioning on CX (the blank allele at locus C), and they mostly disappear for conditioning on C1 to C5. (3) Subpopulations involving C3 or C4 alleles exhibit the significant new combinations A33B17 and A2B15. (4) The B, C loci have a higher total linkage disequilibrium than A, B and A, C; more than expected by mapping distance relationships. (5) The total linkage disequilibrium was significantly larger for conditioning on CX compared to CX (non‐CX), but smaller for the population conditioned by {C3, C4}.A number of interpretations of the results with respect to heterogeneity classifications of populations are discussed.
Research on molecular mechanisms ofMcArdle's disease (muscle glycogen phosphorylase deficiency)
Authors: DAEGELEN‐PROUX D. , KAHN A. , MARIE J. , DREYFUS J.‐C. 
Published: September 2007

SUMMARYMcArdle'@ disease is due to the lack of activity of muscle glycogen phosphorylase. We investigated the presence of an inactive protein by two techniques:(a) tridimensional protein maps, using a modification of the originalO'Farrell technique allowing location of phosphorylase.(b) Purification of enzyme from crude muscle extracts, using an immunoaffinity micro‐chromatographic procedure.Protein maps of three patients were obtained. No protein was detected at the normal (97 K) position of phosphorylase but 70 and 60 K spots were visible. Results of enzyme purification by immunoaffinity were negative for one patient, whereas a small band of phosphorylase‐like material was detected in the other. Our results confirm the molecular heterogeneity of the disease.We think such methods might be useful for investigating other genetic diseases.
Biochemical characterization of the genetic variants of human phosphoglycolate phosphatase (PGP)
Authors: TURNER V. S. , HOPKINSON D. A. 
Published: September 2007

SUMMARYPhosphoglycolate phosphatase (PGP) exhibits a wide range of activities in normal human red cells.Analysis of blood from 57 individuals of known PGP phenotype revealed no correlation between enzyme activity, electrophoretic phenotype or 2,3‐DPG concentration. Neither was there evidence of variation in Km, heat stability, pH optimum or molecular size among the various electrophoretic phenotypes. However, human red cell PGP exhibits high (0‐24 mM) and low (0‐05 mM) Km values for phosphoglycolate irrespective of phenotype and this requires further analysis.
Glucose dehydrogenase polymorphism in man
Authors: KING J. , COOK P. J. L. 
Published: September 2007

SUMMARYAn isoelectric focusing method for human GDH is described which reveals seven GDH phenotypes. Family studies demonstrate that the variation is genetically determined by three alleles at an autosomal locus with gene frequencies GDH1=0723, GDH2= 0‐194, GDH3= 0083. Linkage analysis shows that GDH may be closely linked to PGD on chromosome 1.
Phenotypically normal individuals with an inversion (X) (p22q13) and the recombinant (X), dup q
Authors: BUCKTON K. E. , NEWTON M. S. , COLLYER S. , LEE M. , SPOWART G. , SEABRIGHT M. , SANGER R. 
Published: September 2007

SUMMARYTwo families are described in which there is an inv(X) (p22ql3) which has been transmitted for three generations. In one family (K482), no recombinants have been recovered and the inversion can be traced to a female born in 1839. In the second family (K491), a recombinant (X), dup q, has been recovered in a normal fertile woman. In both families the inverted X appears to be carrying the Xg allele. Despite extensive family studies no common ancestor has been found for the two families.The pattern of DNA synthesis has been studied in those individuals who are karyotypically 46, X, inv(X) (p22ql3) and 46, X, rec(X)dup q, inv(X) (p22ql3); the selection of the abnormal as the late synthesizing X chromosome is random in the former and total in the latter. In some cells the two long arms of the recombinant X chromosome showed asynchrony of DNA replication.
Cytogenetic recognition of chromosomal duplication [dup(l)(p31.4 ‐→ p22.1)] and the detection of three different alleles at the PGM1 locus
Authors: COUSINEAU A. J. , HIGGINS J. V. , HACKEL E. , WATERMAN. D. F. , TORIELLO H. , CARLILE P. A. , COOK P. J. L. 
Published: September 2007

SUMMARYA boy with a duplication of the region lp31.4 → 1p22.1 has the PGM1 phenotype 2+2‐l+.
Factors influencing age at onset and duration of survival in Huntington's chorea
Authors: NEWCOMBE R. G. , WALKER D. A. , HARPER P. S. 
Published: September 2007

SUMMARYLife table techniques permit a more appropriate assessment of the effect of such factors as sex, line of transmission, birth cohort and kindred upon the age at onset and the duration of survival subsequent to onset in Huntington's chorea.
X‐linkage and genetic heterogeneity in bipolar‐related major affective illness: reanalysis of linkage data
Authors: RISCH N. , BARON M. 
Published: September 2007

SUMMARYIt has been suggested that an X‐linked dominant allele operates in the genetic transmission of bipolar (manic‐depressive) illness. Linkage studies with X‐chromosome markers have remained inconclusive, showing both positive and negative results. Some of the ambiguity may be attributed to imprecise analytic methods and genetic heterogeneity. In this report, recently published pedigree series are reanalysed for linkage using a systematic method of pedigree analysis (Liped 3) with an accurate age‐of‐onset correction. Linkage heterogeneity is assessed through a two‐recombination fraction heterogeneity test suggested by Smith (1963). The results are as follows: (1) Close linkage of bipolar illness to colourblindness (deutan and protan) and glucose‐6‐phosphate dehydrogenase deficiency appears to be present in some pedigrees, with estimated recombination fractions of θ= 0.05 and 0.00, respectively; (2) Linkage with the Xg blood group cannot be supported. These results are consistent with known linkages on the X chromosome.
The response of cells from patients with Huntington's chorea to mutagen‐induced chromosome damage
Authors: EVANS H. J. , VIJAYALAXMI  , NEWTON M. S. 
Published: September 2007

SUMMARYCultured blood lymphocytes from 15 patients with Huntington's chorea (HC) and matched controls were exposed to a series of graded doses of mitomycin C and ethyl methane sulphonate and examined for the incidence of sister chromatid exchange (SCE). The spontaneous SCE levels did not differ between HC patients and controls and although cells from the majority of HC patients showed a slightly enhanced response to SCE induction by the mutagens, the enhancement was small and significant only on the pooled data. Cultures from 4 HC patients and controls were exposed to a graded series of X‐ray exposures and no difference was observed in the spontaneous aberration frequencies between HC cells and controls, or in their response to aberration induction by X‐rays. Skin fibroblast cultures derived from three HC patients, two xeroderma pigmentosum patients and two healthy controls were exposed to MMC and the levels of unscheduled DNA synthesis determined. There was no difference between the response of HC cells and normal controls, although such synthesis in the xeroderma cells was severely depressed. It is concluded that: (i) fibroblasts and lymphocytes from HC patients show a normal response to the three mutagens studied; (ii) there is no evidence for any defect in processes involved in repairing the lesions induced; (iii) the slightly elevated response of HC lymphocytes to SCE induction may reflect the presence of a different proportion of a slightly more sensitive T cell sub‐set in HC patients, and (iv) HC cells do not show a hypersensitivity to mutagens that could be used as a basis for diagnosis.
Evolutionary trees and admixture: phylogenetic inference when some populations are hybridized
Authors: LATHROP G. M. 
Published: September 2007

SUMMARYMaximum likelihood estimation of admixture parameters and divergence times for an evolutionary tree in which some populations may be hybridized is developed. A test of treeness against the alternative of hybridization using a hierarchy of admixture models is proposed as an adjunct to the goodness‐of‐fit test suggested by Cavalli‐Sforza & Piazza (1975). The method is illustrated by an application to gene frequency data from Makiritare Indian villages in southern Venezuela.
Regulation of expression of liver‐specific enzymes
Authors: KIELTY C. M. , POVEY S. , HOPKINSON D. A. 
Published: September 2007

Summary1. The expression of twelve liver‐specific enzymes was analysed in twenty‐one independent rat hepatoma x human somatic cell hybrids, and in some cases up to forty‐one subclones were also tested.2. Seventeen hybrids continued to express most of the rat liver‐specific enzymes and in some cases human isozymes of glutamate‐pyruvate transaminase, α‐glycerophosphate dehydrogenase, guanine deaminase, alcohol dehydrogenase and pyruvate kinase were clearly identified.3. Analysis of the segregation of the human liver‐specific enzymes in these hybrids led to the assignment of human GPT to chromosome 8 (previously reported, Kielty, Povey & Hopkinson, 1982) and suggests the assignment of human GPD1 to chromosome 12.4. The expression of the various liver‐specific enzymes in these hybrids appeared to be controlled by independent regulatory mechanisms.5. Four unusual reverse segregant hybrids were also analysed, and in these no liver‐specific enzyme activity was demonstrable.
Gene order and localization of enzyme loci on the short arm of chromosome 1
Authors: CARRITT B. , KING J. , WELCH H. M. 
Published: September 2007

SummaryAnalysis of hybrids containing different rearrangements involving human chromosome 1 suggests that GDH and ENO1 are distal to PGD, and that all 3 loci are distal to 1p36.13. Evidence is presented indicating that FUCA and AK2 are in 1p34.
Analysis of linkage relationships of Co, Jk and K with each other and with chromosome 2 loci ACP1 and Km
Authors: LEWIS M. , KAITA H. , PHILIPPS S. , STEINBERG A. G. , GIBLETT E. R. , ANDERSON J. E. 
Published: September 2007

SummaryLinkage analyses of locus pairs involving ACPI, Co, Jk, K and Km indicate: probable linkage between Co and Jk (&#x007a;̂=+3.80 at θ= 0.29); possible linkage between Jk and Km (z =+1.93 at θ= 1.30); a mild hint of linkage between Co and K 9z=+1.01 at θ= 0.30); inadequate information for Co: Km linkage for K: Jk, K: Km, ACPI: Jk, ACPI: K and ACPI: Km. The compiled information does not allow assignment of Co, Jk or K to chromosome 2.
Bias of the estimated recombination fraction and lod score due to an association between a disease gene a marker gene
Authors: CLERGET‐DARPOUX F. 
Published: September 2007

SummaryAn association between a recessive disease gene and a biallelic codominant linked marker is shown to induce some bias in the estimation of the recombination fraction by the lod score method. We demonstrate that ignoring the association may lead to an underestimate of the true recombination fraction and the lod score.
Extensions to multivariate normal models for pedigree analysis
Authors: HOPPER J. L. , MATHEWS J. D. 
Published: September 2007

SummaryLange, Westlake & Spence (1976) used the assumption of multivariate normality to apply a likelihood method to the analysis of quantitative traits measured over pedigrees. We now introduce a test of the assumption of multivariate normality and methods for the detection of outlying families and outlying individuals. We also introduce a method for the estimation of effects of measured genetic markers as variance components, a flexible parameterization to estimate effects of shared family environment, and a method to allow for the ascertainment of pedigrees through probands. These innovations have been applied using numerical methods for maximization of the likelihood. Simulation studies and available theory suggest that the likelihood ratio criterion used in significance testing follows the expected asymptotic distribution with sample sizes encountered in typical applications.
Immunological detection of the sixth complement component (C6) following flat bed polyacrylamide gel isoelectric focusing and electrophoretic transfer to nitrocellulose filters
Authors: Whitehouse D. B. , Putt W. 
Published: September 2007

SummaryA method for the electrophoretic transfer of C6 molecules to a nitrocellulose filter is described. The protein is detected by the use of anti‐C6 antibodies and a peroxidase conjugated antibody. Using this method typical isoelectric patterns of C6 variant phenotypes are found. Inheritance and population data are presented. Three rare structural variants, one of which appears to be previously unreported, were discovered among a sample of 202 individuals. The method is discussed from the viewpoint of its flexibility and its value as an additional tool for revealing inherited variations in structural gene products.
Analysis of human erythrocyte 5‘‐nucleotidases in healthy individuals and a patient deficient in pyrimidine 5’‐nucleotidase
Authors: Swallow D. M. , Aziz I. , Hopkinson D. A. , Miwa S. 
Published: September 2007

SummaryElectrophoretic and quantitative analysis of pyrimidine 5′‐nucleotidase in human erythrocytes from healthy individuals and a patient deficient in pyrimidine 5′‐nucleotidase, using a range of substrates, has shown that the patient has a marked deficiency with UMP, CMP and dCMP as substrates but near normal levels of activity with dUMP and dTMP as substrates. The observations suggest that two separate structural gene loci coding for distinct 5′‐nucleotidases with similar electrophoretic mobility exist in man. The genetic determination of these enzymes seems therefore to be homologous with that found in rodents.
The impact of legal termination of pregnancy and of prenatal diagnosis on the birth prevalence of Down syndrome in Denmark
Authors: MIKKELSEN M. , FISCHER G. , HANSEN J. , PILGAARD B. , NIELSEN J. 
Published: September 2007

SummaryA considerable reduction in number of livebirths for mothers over 35 was observed in Denmark from 1960 to 1980. Birthrates for those aged 35–39 fell by 58.8%, for those aged 40–44 by 78%. In 1979–1980 100 infants with Down syndrome were born among 116757 newborns, a birth prevalence of 0.86 per 1000, which was significantly lower than the incidence of 1.17 per 1000 when the prenatally diagnosed cases were included. The reduction was noticeable for the age group over 35 where it fell to 1.89 per 1000 for mothers 35–39 and 6.48 per 1000 for mothers over 40.The utilization of prenatal diagnosis was 72 per 100 livebirths for women 35 and older in the Copenhagen area and 56 per 100 livebirths for the rest of the country, with differences in different areas.The number of induced abortions for women 35 years and older was 9265 against 6597 livebirths. The estimated number of Down syndrome cases averted by unrestricted abortion was 61, twice the number prevented by amniocentesis (31), with the greatest impact for mothers over 40.An increased risk of Down syndrome for the age group 35–39 was observed when liveborn and prenatal cases were considered together showing an incidence of 6.89 per 1000, with the highest incidence in the Copenhagen area, 8.70 per 1000, more than double the incidence of 3.04 observed in Copenhagen from 1960 to 1971, for the same age group.
The affected sib method. II. The intermediate model
Authors: LOUIS E. J. , THOMSON G. , PAYAMI H. 
Published: September 2007

SummaryAn iteration procedure is outlined which uses HLA haplotype sharing data from sib pairs in which both sibs have the disease of interest. The procedure allows estimation of the degree of dominance of the HLA linked ‘disease’ allele, and its frequency in the population, for intermediate models where it is assumed that individuals who do not have at least one copy of the ‘disease’ allele do not contract the disease. Parameter estimates from sib‐pair data on multiple sclerosis, insulin dependent diabetes mellitus, haemochromatosis, coeliac disease juvenile rheumatoid arthritis, and Graves' and Hasimoto's diseases are given.
Genetic polymorphism of the LW blood group system
Authors: SISTONEN P. , GREEN C. A. , LOMAS C. G. , TIPPETT P. 
Published: September 2007

SummaryFamily studies of rare LW(a‐b+) propositi confirm the recent finding based on frequency studies that the LW blood groups are polymorphic in Finland (Sistonen & Tippett, 1982); they are controlled by two alleles LWa (0.97) and LW* (0.03) independent from most other common blood group loci. Loci scores for LW and the loci for 27 markers are presented.
Immunological and biochemical characterization of the human alcohol dehydrogenase χ‐ADH isozyme
Authors: Adinolfi A. , Adinolfi M. , Hopkinson D. A. 
Published: September 2007

Summary1. The recently identified χ‐ADH isozyme was purified from human liver and used to raise immune sera.2. The χ form of ADH showed no structural resemblance to the ADH1, ADH2 and ADH3 (class I) or ADH4 (class II) isozymes, as judged by its immunological properties.3. χ‐ADH was found in most human tissues including fetal specimens of 16 weeks gestational age and showed a preference for long chain primary alcohols with a double bond in the β position.4. We conclude that the locus, designated ADH5, encoding the χ isozyme has a separate evolutionary origin from the other ADH genes.
A two‐susceptibility‐allele model for genetic diseases and associated marker loci: differences and similarities to a one‐s‐allele model
Authors: Falk C. T. 
Published: September 2007

SummaryA model for genetic diseases and associated markers is defined where two distinct susceptibility alleles are possible, each associated with a different marker allele. Marker genotype distributions in a disease population are then expressed in terms of haplotype frequencies and penetrance parameters. It is shown that, if the heterozygote with two different disease alleles has a higher penetrance than the two disease homogzygotes, the observed to ‘Hardy‐Weinberg‐expected’ ratio of associated marker genotypes (the α/β ratio of Falk, Mendell & Rubinstein, 1983) will always be greater than or equal to one. When all disease penetrances are equal, the model becomes indistinguishable from a recessive one‐s‐allele model with α/β= 1.Application of these observations to several data sets for insulin dependent diabetes mellitus suggests the possibility that different marker genotype distributions in different samples may be due to different penetrances of the disease genotypes in the samples. If a particular environment causes the heterozygote disease genotype (with two different disease alleles) to have the highest penetrance, the marker genotype distribution would be compatible with the 2‐s‐allele model. In other environments where the three disease genotypes have essentially equal penetrances, the marker distribution would be compatible with the 1‐s‐allele model.
On the lod score method in linkage analysis
Authors: Chotai J. 
Published: September 2007

SummaryGenetic epidemiology deals with the interaction of environmental and genetic determinants in common diseases. Linkage analysis is an important branch of this field. The current practice of claiming linkage between two genetic loci when the maximum lod score z(θ) exceeds 3 has not received theoretical justification, whether considered as a sequential or as a fixed sample size test. Within the framework of significance testing, Wald's (1947) formulae are not applicable to allow this procedure a sequential interpretation. Considered as a fixed sample size test, we find that a X2approximation would instead be very adequate. Since repeated significance testing is performed on linkage data, the nominal significance level should be more stringent for each test than the overall level. Some recent developments in group sequential trials by Pocock (1977) and in repeated significance testing by Woodroofe (1979) seem to indicate that the critical value of the maximum lod score should lie roughly between 0·9 and 3·3, depending on the maximum number of repetitions anticipated, on whether the significance level is desired to be 0·05, 0·01 or 0·001, and on whether the test is derived from a one‐sided or a two‐sided consideration. In terms of the group sequential approach, if a maximum of twenty repetitions is allowed, if z(θ) > log10A is considered as a one‐sided test and assumed to be symmetric when linkage is absent, then the type I error is approximately given by 1/A. We also treat the confidence interval approach for exclusion of unlikely recombination values.
Assignment of the human gene for δ aminolevulinate dehydrase to chromosome 9 by somatic cell hybridization and specific enzyme immunoassay
Authors: BEAUMONT C. , FOUBERT C. , GRANDCHAMP B. , WEIL D. , N'GUYEN VAN CONG , GROSS M. S. , NORDMANN Y. 
Published: September 2007

SummaryA non‐competitive enzyme immunoassay specific for δ aminolevulinate dehydrase has been devised and applied to rodent–human hybrid cell lines. Two different conditions have been used, one specific for the human enzyme and the other indicative of both rodent and human enzymes. The ratio of the values obtained under the two conditions was used to discriminate between positive and negative clones. By this method the gene for ALA dehydrase has been assigned to chromosome 9.