bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic analysis workshop II: Summary
Authors: Maccluer Jean W. , Falk Catherine T. , Spielman Richard S. , Wagener Diane K. 
Published: June 2005

AbstractThe Second Genetic Analysis Workshop was held October 30, 1983, at the American Society of Human Genetics meetings in Norfolk, Virginia. Ten groups of investigators analyzed three sets of pedigrees generated by computer simulation. A summary of the workshop is presented.In this overall description by the workshop organizers, the rationale for the choice of problems and the characteristics of the three data sets are discussed, and the ten analyses are briefly summarized and compared. Following this general summary are brief descriptions of the analyses of each group of workshop participants, in alphabetical order by senior author.
Genetic analysis workshop II: Results of segregation analyses using POINTER and linkage analyses using LIPED
Authors: Cox Nancy J. 
Published: June 2005

AbstractGenetic Analysis Workshop II Problems 2 and 3 were analyzed using the segregation analysis program POINTER and the linkage analysis program LIPED. Results of the segregation analyses were acceptable with respect to both parameter estimation and hypothesis testing. Results of the linkage analyses were also good. Although it was noted that the linkage and population association data were sometimes compatible with more than one hypothesis, the correct relationships among the trait and marker loci were generally among those found compatible with the data.
Genetic analysis workshop II: Pedigree analysis of a binary trait without assuming an underlying liability
Authors: Hopper J. L. , Hannah M. C. , Mathews J. D. 
Published: June 2005

AbstractA model for concordance in a binary measure that does not rely on the assumption of an underlying latent liability dichotomized about a threshold has been demonstrated for twin pairs [Hannah et al, 1983]. It is extended here to pedigrees of arbitrary structure by making an assumption that is, for small incidence rates, almost equivalent to postulating that relative risks are multiplicative. The model is applied to the workshop data to determine the extent to which the known structure of the simulated models can be recovered.
Genetic analysis workshop II: Combined segregation, linkage, and association analysis
Authors: Morton N. E. , Sherman S. L. , Maclean C. J. , Yee S. , Lew R. 
Published: June 2005

AbstractA combined segregation, linkage, and association analysis using the program COMBIN was performed on the simulated pedigree data prepared for the Second Genetic Analysis Workshop. The model used in COMBIN is described and the presented results illustrate its effectiveness in the analysis of such data. Linkage analysis was performed and maps for each linkage group are presented.
Genetic analysis workshop II: Segregation and linkage analysis
Authors: Namboodiri Kadambari K. , Kaplan Ellen B. 
Published: June 2005

AbstractFamilial segregation and linkage analyses were performed on two sets of the Genetic Analyses Workshop II data. The salient features of the mode of inheritance of the disease trait and its linkage/association with polymorphic markers and also marker‐marker linkages were delineated using statistical‐genetic techniques.
A test of nonrandom segregation
Authors: Badner Judith A. , Chakravarti Aravinda , Wagener Diane K. , Rao D. C. 
Published: June 2005

AbstractWithin a family, associations between a disease and a marker locus are often inferred when affected offspring share marker alleles more often than is expected by chance. Generally, this is due to nonrandom parental transmission of marker alleles and specifically could be due to linkage, epistatic gene action, or segregation distortion at the marker locus. In this paper, we discuss the statistical properties of a general test of nonrandom segregation of a marker gene. The exact probability distribution of the test under the null hypothesis of random segregation is derived, as is the distribution under the alternative hypothesis of genetic linkage. We compute the mean and variance of these distributions as a means of judging the adequacy of random segregation to explain disease‐marker data but also provide a method for computing the exact significance value under the null hypothesis. These methods have been utilized for studying HLA segregation in families with tuberculoid leprosy. On the assumption that this type of leprosy is autosomal recessive, we find evidence that a gene controlling susceptibility to infection by Mycobacterium leprae resides on human chromosome 6, approximately 13 map units away from the HLA locus in males.
Resolving genetic models for the transmission of schizophrenia
Authors: McGue M. , Gottesman I. I. , Rao D. C. , Spence M. Anne 
Published: June 2005

AbstractAlthough family studies have consistently reported elevated rates of schizophrenia among the relatives of schizophrenics, the exact nature of the transmission of the disorder remains uncertain. Genetic models hypothesized to explain the transmission of schizophrenia include the generalized single locus and multifactorial threshold models. Here we briefly describe these models and test their goodness‐of‐fit to a single data set on the pooled morbid risks of schizophrenia among the relatives of schizophrenic probands in nine different classes of relatives with five different degrees of genetic relatedness. The generalized single locus model is rejected, while a pure polygenic threshold model does fit the observed risks. Allowance for environmental sources of familial resemblance under the multifactorial threshold model significantly improved the fit of the model to the data. An application of the multifactorial model to family data on tuberculosis is also reported. For tuberculosis, a strong familial environmental but not genetic effect was found, consistent with the known infectious etiology of this condition, showing that the finding of a strong genetic effect upon schizophrenia is not a necessary bias of these methods of analysis. The implications of these results for the search for major gene effects in schizophrenia are discussed.
Efficiency of lod scores for representing multiple locus linkage data
Authors: Maclean C. J. , Morton N. E. , Lew R. , Rao D. C. 
Published: June 2005

AbstractThe problem of compact, fully efficient representation of multilocus data has not yet been solved. Lod scores can be used to map multilocus data, but because of certain statistical problems, this method loses some information. However, simulation studies show that for distances less than 10 or 20 cMo, where there is little danger of huge overestimates of distance, the lod score method yields estimators just as good as maximum likelihood (ML). Since short distances are the most important, the lod method is quite efficient. Its main drawback is misrepresentation of the likelihood under wrong gene orders. This problem can be ameliorated with a single multipoint calculation under each order. Thus, representation of multipoint data with lod scores can be very practical.
Genetic analysis workshop III: Summary
Authors: Maccluer Jean W. , Falk Catherine T. , Wagener Diane K. 
Published: June 2005

AbstractGenetic Analysis Workshop III (GAW III) was held October 31, 1984 at the American Society of Human Genetics meetings in Toronto, Ontario. Prior to the workshop, a set of 150 computer‐simulated pedigrees was distributed. Individuals in the artificial pedigrees were characterized by genotypes at eight marker loci. Twelve groups of investigators analyzed linkage in this data set and submitted results for presentation at the workshop.This summary of GAW III by the members of the workshop organizing committee includes a brief history of the workshops and the rationale for the choice of problems, a description of the method by which the computer‐simulated pedigrees were generated, a brief summary of the analyses of the 12 groups of participants, and a discussion of the general conclusions derived from the workshop and from a preworkshop meeting of participants. Descriptions of the analyses by each of the 12 groups, in alphabetical order by senior author, follow this overall summary.
Genetic analysis workshop III: Multipoint linkage analysis using FAP
Authors: Baur Max P. , Neugebauer Meinhard , Sigmund Martin 
Published: June 2005

AbstractThe family analysis package (FAP), originally designed for the analysis of the multilocus pedigree data of the 9th HLA workshop, was applied to the problem of multipoint mapping and estimation from the simulated data of GAW III. The four‐point analyses performed within the two identified linkage groups yielded correct results.
Genetic analysis workshop III: Multilocus linkage analysis using PAP
Authors: Bishop D. T. , Cannon L. A. , Hasstedt S. J. , Skolnick M. H. 
Published: June 2005

AbstractTwo linkage groups were identified through pairwise linkage analysis using PAP. Three‐locus analysis confirmed the suggested order of the loci within the linkage groups and was used to assess the strength of the conclusions. Strategies for improving the efficiency of linkage analysis are discussed.
Genetic analysis workshop III: Use of multidimensional scaling in chromosome mapping
Authors: Donald J. , Sturt E. , Der G. , McCusker K. 
Published: June 2005

AbstractTwo‐point methods were used throughout. Male and female lod scores were calculated using LIPED. Edwards' programs, ZLODS and OBM, were used for joint analysis of the lod scores. ZLODS estimates recombination fractions. OBM calculates the likelihood and estimates the map distances for a given ordering of loci. Since OBM will only analyze a specified ordering, multidimensional scaling was used as a general method for establishing linkage groups and likely orderings within them.
Segregation analysis of dopamine‐beta‐hydroxylase (DBH) and catechol‐o‐methyltransferase (COMT): Identification of major locus and polygenic components
Authors: Goldin Lynn R. , Rao D. C. 
Published: June 2005

AbstractEnzymes of catecholamine metabolism, plasma dopamine‐beta‐hydroxylase (DBH), and erythrocyte catechol‐O‐methyltransferase (COMT) were each previously shown to be transmitted as single codominant loci in a sample of approximately 30 multigenerational families that were analyzed with the single major locus model. Here, both major locus and polygenic hypotheses are tested by applying the mixed model of analysis to the identical samples, after breaking the families into two‐generation units. For plasma DBH, the most parsimonious model is a dominant major locus (ie, high values dominant to low values) accounting for 41% of the variance and a polygenic component accounting for 25% of the variance. For erythrocyte COMT, the most parsimonious model is a dominant major locus accounting for 56% of the variance and a polygenic component accounting for 27% of the variance. The major locus for COMT has been supported by previous biochemical studies. The major locus for DBH is supported by the finding from our previous study of possible linkage to the ABO locus. Further biochemical and molecular genetic investigations are needed to better define the genetic loci determining the activity of these enzymes.
Construction of conditional lod tables from multiple‐locus linkage data
Authors: Maclean Charles J. , Lew Ruth , Yee Shirley , Rao D. C. 
Published: June 2005

AbstractAlthough multipoint linkage data are becoming quite common, economical and efficient methods for presenting these data are not yet in use. Tables giving the full likelihood function would be very voluminous, whereas reduction to standard lods destroys part of the information. We suggest a special lod table representation which preserves nearly all the information about both gene order and genetic map distance at a great reduction in data presented. Conditional lods, coined “c‐lods” to distinguish them clearly from ordinary lods, are calculated for distances between each adjacent pair of loci, with all distances among other loci in the system conditionally optimized. Thus, in an n‐locus system, conditional lods are presented for the n − 1 adjacent pairs of loci only.The principal reason for reporting lod scores is the potential for combining data from separate studies to reach conclusive evidence for linkage and gene order. Because estimates of recombination are different in each set of data, the crux of the problem is to present scores that provide a close approximation to the true likelihood away from maximum likelihood (ML). The sum of conditional lods closely approximates the likelihood throughout the domain. Therefore, conditional lods contribute appropriately when mapping from several sources of data, so contradictory estimates can be reconciled efficiently.
Familial resemblance of bone mass in adult women
Authors: Sowers Maryfran R. , Burns Trudy L. , Wallace Robert B. , Rao D. C. 
Published: June 2005

AbstractBone mass may be so reduced in some individuals as to be characterized as osteoporotic, with resulting fracture, particularly of the proximal femur, vertebrae, or wrist. We identified 34 mother‐daughter sets (n = 70) and 29 sibling sets (n = 59) from a community study of bone mass correlates to assess the degree of resemblance in bone mass within and between generations. We hypothesized that if between‐ and within‐generation correlations of bone mass in first‐degree relatives were of sufficient magnitude, then an important genetic influence in osteoporosis might be considered. Bone mass was measured at the distal radius using a single‐beam photon absorptiometer. Height, weight, triceps skinfold thickness, and mid‐arm circumference were also measured, and the latter two measurements used to compute humeral muscle area. We identified a significant resemblance in height among the sibling sets. We found no consistent evidence for significant resemblance of bone mass among women when considering mother‐daughter sets or sibling sets.
Studies on an isolated West Indies population: IV. Genetic study of hearing loss
Authors: Bonaïti Catherine , Demenais Florence , Bois Etienne , Hochez Joelle , Rao D. C. 
Published: June 2005

AbstractHearing troubles were found to be very frequent among inhabitants of French origin in a small Caribbean island. Segregation analysis of hearing loss was performed in 165 complete nuclear families and revealed that familial aggregation could be entirely explained by a single recessive gene with high frequency (0.40). Homozygous individuals for this gene would probably be more susceptible to ototoxic agents than other individuals. High frequency of this gene may be due to a founder effect.
Familial aggregation of cancer in Laredo, Texas: A generally low‐risk Mexican‐American population
Authors: Weiss Kenneth M. , Chakraborty Ranajit , Smouse Peter E. , Buchanan Anne V. , Strong Louise C. , Rao D. C. 
Published: June 2005

AbstractGenealogies for the Mexican‐American city of Laredo, Texas, have been assembled by computer from individual civil and church records of birth, marriage, and death. Documentation is available on vital events in the lives of over 300,000 individuals, about 80% of the city population from 1870–1981. These data were collected to determine the degree to which death from cancer is more clustered in families than would be expected by chance alone; methods specific to this data base have been developed to accomplish this task. A statistically significant excess of familial cancer was observed overall when all cancer sites were pooled, but no evidence was observed for excess familial risk at single sites except for breast cancer and perhaps for ovarian cancer. The excess of breast cancer risk is comparable to that observed in other populations. A few site‐combinations manifest excess familial risk, most notably those involving and dominated by breast cancer and certain digestive system sites. We do not confirm the degree of familiality observed elsewhere for cancers of the lung, colorectum, stomach, or other sites in this generally low‐risk population. Even where we find evidence of excess risk, the degree of excess is small and the number of multiply affected families too small to test etiologic models by segregation analysis. The absence of excess familial risk does not appear to be due to inadequate numbers of cases, since breast cancer is familial with no more occurrences in Laredo than other sites. These results differ to some extent from those found in a similar study of Utah Mormons, but it is unclear whether this is because of differences in risk patterns or statistical properties of the analytic methods used in the two studies.
Human parotid proline‐rich proteins: Correlation of genetic polymorphisms to dental caries
Authors: Yu Pao‐Lo , Bixler David , Goodman Patricia A. , Azen Edwin A. , Karn Robert C. , Rao D. C. 
Published: June 2005

AbstractParotid saliva contains a variety of proline‐rich proteins. This study found that, among 306 children between the ages of 5 to 15 years, there is a significant increase in the decayed‐missing‐filled tooth surface (DMFS) score of the permanent teeth with age in children with the specific proline‐rich protein phenotypes Pa and Pr. However, the increase in DMFS score of the permanent teeth of children was significantly greater in children with Pa+ and Pr22 than in those with the other phenotypes (Pa– or Pr11 and Pr12). The previously established close correlation between the Pa and Pr phenotypes and the genetic variants of salivary peroxidase (a powerful antibacterial system in the oral cavity) may provide an explanation for the relationship of certain proline‐rich protein phenotypes to dental caries.
Symptom patterns and causes of somatization in men: II. Genetic and environmental independence from somatization in women
Authors: Cloninger C. Robert , von Knorring Anne‐Liis , Sigvardsson Soren , Bohman Michael , Conneally P. M. 
Published: June 2005

AbstractThe genetic and environmental antecedents of clinically distinct disorders leading to somatization were compared in 807 Swedish men and 859 Swedish women adopted at an early age by non‐relatives. Asthenic somatization, the predominant form in men, was a neurotic disorder associated with a lower incidence of criminality in the somatizers' biological parents than in the biological parents of non‐somatizers of either sex. In contrast, most female somatizers and a minority of men with diversiform somatization had disorders that were associated with a higher incidence of criminality in their biological parents than in other biological parents. Likewise, female somatizers, but not male somatizers, had an excess of alcoholic biological fathers when compared to other adoptees. In addition, different postnatal environmental background factors contributed to the risk for somatization in each sex. These findings support the distinctions among the different types of somatizers and show that the usual causes of somatization are fundamentally different in men and women. This illustrates the utility of the adoption paradigm in resolving genetic and environmental contributions to the familial aggregation of developmentally complex phenotypes.
Log‐linear model analysis of allelic associations
Authors: Aston C. E. , Wilson S. R. , Rao D. C. 
Published: June 2005

AbstractAn approach is outlined for the analysis of nonrandom allelic associations in multilocus systems in a diploid population. The concept of composite link functions in generalised linear model analysis is used to handle the problem of incomplete identification of constituent gametes often encountered in genotypic data for two or more marker loci.
Progress toward resolving the possible linkage of multiple endocrine neoplasia type 2A to haptoglobin and group‐specific loci: Use of restriction fragment length polymorphisms extends exclusion region
Authors: Kidd K. K. , Kidd J. R. , Castiglione C. M. , Pakstis A. J. , Sparkes R. S. , Rao D. C. 
Published: June 2005

AbstractIn an earlier paper, positive but nonsignificant lod scores were found in pair‐wise linkage tests between multiple endocrine neoplasia type 2A (MEN‐2A) and both the haptoglobin (HP) locus on chromosome 16 and group‐specific component (GC) locus on chromosome 4. Recently discovered restriction fragment length polymorphisms for HP and for metallothionein 2 processed pseudogene 1 (MT2P1) near GC have made it possible to carry out a more powerful set of linkage tests with MEN‐2A. This paper reports the results of such linkage analyses employing both pair‐wise and multipoint tests. Close linkage of HP on chromosome 16 and MEN‐2A is excluded. Linkage of MEN‐2A on chromosome 4 with GC is excluded on the MT2P1 side of GC in a 7‐centimorgan interval around MT2P1.
Evidence for linkage between Wilson disease and esterase D in three kindreds: Detection of linkage for an autosomal recessive disorder by the family study method
Authors: Bonné‐Tamir Batsheva , Farrer Lindsay A. , Frydman Moshe , Kanaaneh H. , Rao D. C. 
Published: June 2005

AbstractWilson disease (WD) is an inherited disorder of copper metabolism that affects the brain, liver, and other organs. Our group recently reported close linkage between the locus for WD and a polymorphic red cell enzyme, esterase D (EsD), in a large inbred Israeli‐Arab lineage. We have subsequently studied two unrelated Druze kindreds in order to confirm this linkage and more precisely define the distance between the two loci. The maximum likelihood estimate of recombination was determined to be zero with lod scores of 1.48 and 1.06 in each Druze family, respectively. The combined maximum lod score based on pooled results from the Israeli‐Arab and Druze kindreds is 5.49 at θ = 0.03.WD is one of a few autosomal recessive disorders that has been mapped by classical family study methods. In this paper, the merits for using large, inbred families in linkage studies of rare recessive disorders are discussed. Major considerations for pedigree selection are size and number of constituent nuclear families, number and distribution of affected individuals, and pedigree structure that may provide information for determination of phase between the disease and marker loci.
Genetic etiology of gastric carcinoma: I. Chronic atrophic gastritis
Authors: Bonney George E. , Elston Robert C. , Correa Pelayo , Haenszel William , Zavala Diego E. , Zarama Guillermo , Collazos Tito , Cuello Carlos , Rao D. C. 
Published: June 2005

AbstractScientific evidence has accumulated to show that chronic atrophic gastritis (CAG) is a precursor of gastric carcinoma, especially its intestinal histologic type; thus the etiology of CAG is of interest. Data on 110 families (557 individuals) collected as part of a large cohort from the Narino region of Colombia, South America, are analyzed to determine the familiality of CAG as a risk factor, and the possible involvement of a major gene in its etiology. We found that age and having an affected mother are important risk factors. In the sample, 45% are affected; 56% of individuals above 30 are affected, whereas only 28% of those 30 and under are affected; 48% of those with affected mothers are affected, but only 7% of those with unaffected mothers are affected. A positive spouse association was confounded with age. Sex and an affected father are not significant risk factors. The genetic (segregation) analysis showed Mendelian transmission of a recessive autosomal gene with penetrance dependent on age and mother's CAG status. Homozygous recessives account for an estimated 61% of the sampled population and have penetrance reaching 72% at age 30 if the mother is affected, and 41% if the mother is not affected. Carriers and non‐carriers, who make up an estimated 39% of the sampled population, have an appreciable estimated risk after age 50. The environment, particularly diet, as the sole determinant of CAG needs re‐evaluation; some combined action of genes and environment seems more plausible.