bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multipoint linkage analysis of spinocerebellar ataxia and markers on chromosome 6
Authors: Haines J. L. , Trofatter J. A. , Rao D. C. 
Published: June 2005

AbstractHeterogeneity among the spinocerebellar ataxias (SCA) has been shown on clinical, biochemical, and genetic criteria. Among the autosomal dominant SCAs, several kindreds have shown loose linkage to the HLA loci on chromosome 6, while linkage in other kindreds has been rejected. The advent of multipoint linkage analysis allows the use of several marker loci simultaneously, thus increasing the amount of usable information. We have reanalyzed linkage data from a large kindred with SCA and provide evidence for a telomeric location of the SCA gene in this family. Knowledge of the relative gene location will ease the identification of the SCA gene by reducing the size of the chromosomal regions that must be examined.
Etiological heterogeneity in Hodgkin's disease: HLA linked and unlinked determinants of susceptibility independent of histological concordance
Authors: Chakravarti Aravinda , Halloran Susan L. , Bale Sherri J. , Tucker Margaret A. , Rao D. C. 
Published: June 2005

AbstractForty‐one multiplex families, from published sources and new data from the National Cancer Institute, segregating for Hodgkin's disease and HLA, have been studied. A reanalysis of these data strongly suggests a recessive mode of inheritance for susceptibility to Hodgkin's disease. The HLA haplotype sharing data between affected relatives demonstrate that approximately 60% of cases in multiplex families are due to an HLA‐linked susceptibility gene, the remaining 40% being due to other familial factors. The data clearly support the hypothesis of etiological heterogeneity for Hodgkin's disease, with both HLA‐linked and HLA‐unlinked factors being responsible. Finally, there is an increased concordance of histological types between affected relatives, but this concordance seems independent of HLA sharing.
Early onset periodontitis: A comparison and evaluation of two proposed modes of inheritance
Authors: Long Jeffrey C. , Nance Walter E. , Waring Patsy , Burmeister John A. , Ranney Richard R. , Rao D. C. 
Published: June 2005

AbstractTwo rare types of familial periodontitis, a localized form usually diagnosed in late adolescence, and a more generalized form with a latter mean age of diagnosis, have been analyzed with respect to genetic models currently favored in the dental literature. These include autosomal recessive and X‐linked dominant (partial penetrance) inheritance. Since there is variation in severity, extent, age of onset, altered sex ratio of affected individuals, and a low population prevalence, it is not surprising that genetic mechanisms heretofore have not been revealed.We have compared the likelihoods of 33 kindreds ascertained through affected probands under the above genetic models. Our findings include (1) several families in which both forms of early onset periodontitis co‐occur, making it unlikely that the clinical varieties of the disease have unrelated genetic causes; (2) the autosomal recessive model is far more likely than the X‐linked dominant model. The superiority of the recessive hypothesis arises from the fact that there are only a few instances of affected individuals having affected parents and because the skewed sex ratio is shown to be incompatible with X‐linked inheritance. These conclusions are largely insensitive to the assumptions of the analysis. We conclude that the X‐linked dominant hypothesis is inadequate, and while the autosomal recessive model is by no means proven, it is clearly favored.
A family study of panic disorder
Authors: Hopper John L. , Judd Fiona K. , Derrick Peter L. , Burrows Graham D. , Rao D. C. 
Published: June 2005

AbstractPanic disorder, as defined by the DSM III diagnostic criteria, was diagnosed in 117 probands for whom age of onset ranged from 10 to 59 years, with a mean of 26.6 years. Diagnosis of parents and siblings was based on interviews with the probands, and only those with “definite” panic disorder by the FISC criteria were considered to be affected. The pattern of concordances for panic across different groups of relatives was estimated concurrently by a log‐linear model for binary pedigree data, assuming different values for the cumulative risk. When an adjustment for age was made, based on the age of onset of probands, there was no significant difference between parent‐offspring concordance and sibling concordance. There was a negative, but not significant, concordance between spouse pairs. Assuming the lifetime cumulative risk was 1.9% for males and 4.7% for females, values considered appropriate for this population, our model predicted that the presence of an affected parent or sibling incurs an approximately five times increase in the risk of developing panic disorder. Our model assumes in effect that this risk is multiplied for each further affected relative. Although the common concordance across relationship groups is consistent with a genetic hypothesis, it can also be explained by common family environmental factors. There is a need for further pedigree studies, using twins and relatives, for example, and reliable information on the cumulative risk.
Genetic epidemiology of cleft lip with or without cleft palate in the population of Hawaii
Authors: Chung C. S. , Mi M. P. , Beechert A. M. , Borecki I. B. 
Published: June 2005

AbstractOrientals consisting of Japanese, Chinese, Koreans, and Filipinos are clearly at higher risk for cleft lip with or without cleft palate [CL(P)] than whites, Puerto Ricans, and Hawaiians/part‐Hawaiians in Hawaii. Using the model of diallele cross, CL(P) incidences in incrosses and outcrosses involving 564,002 live births distributed among 669 mating types were analyzed to study the extent of major gene involvement in the difference in the two groups and to investigate maternal effect in the etiology of CL(P). CL(P) cases excluding syndrome cases were classified into two types: all CL(P) cases and CL(P) cases without additional malformations. For either type there was no evidence to suggest that simple major gene plays a dominant role in accounting for racial differences as measured by deviations from additivity in the hybrids. For CL(P) cases without additional defects, a negative “maternal effect” was detected in Filipinos such that higher risk for this racial group depends on when the father is Filipino. Implications of the findings are discussed.
Possible heterogeneity in the segregation pattern of breast cancer in families with bilateral breast cancer
Authors: Goldstein AM , Haile RWC , Hodge SE , Paganini‐Hill Ann , Spence MA , Rao D. C. 
Published: June 2005

AbstractWe investigated the segregation pattern of breast cancer in families with bilateral breast cancer, classifying families with respect to menopausal status (premenopausal versus postmenopausal) and the interval between diagnosis of the two primary tumors in the probands. Probands were “synchronous” if both primaries were diagnosed within 1 year; “asynchronous” if the interval was at least 2 years. Results for four complex segregation analyses are here presented; the findings support heterogeneity in the transmission of breast cancer. In the asynchronous premenopausal‐cases‐only analysis, a dominant Mendelian gene can explain the breast cancer pattern. A recessive gene is sufficient to describe the breast cancer distribution in the synchronous premenopausal‐cases‐only analysis. The synchronous all‐cases and the asynchronous all‐cases analyses add postmenopausal cases of breast cancer to the premenopausal ones, considering any case to be affected. In the asynchronous all‐cases analysis, neither the single‐locus model nor the mixed model (that is, a major locus plus other factors, genetic and/or cultural) without generation differences in heritability can be rejected by the unrestricted mixed model with generation differences in heritability. For the synchronous all‐cases analysis, a mixed model with generation differences in heritability is necessary to explain the breast cancer transmission. Potential sources of error and possible interpretations are discussed.
Genetic analysis of IDDM: The GAW5 multiplex family dataset
Authors: Baur M. P. , Fimmers R. , Fritsche C. , Hümmelink M. , Neugebauer M. , Acton R. T. , Hodge T. , Barbosa J. , Bertrams J. , Fehsel K. , Kolb H. , Rothe H. , Boehm B. , Cambon‐Thomsen A. , Avoustin P. , Coppin H. , Darnaud J. , Massabie P. , Ohayon E. , de Preval C. , Tauber J. P. , Thomsen M. , Colle E. , MacDonald M. J. , Nevin D. , Gottschall J. L. , Nepom G. T. , Robinson D. M. , Holbeck S. , Palmer J. P. , Nerup J. , Rotter J. I. , Vadheim C. , Rittner C. , Schneider P. , Sheehy M. J. , Cox N. J. , Baker L. , Spielman R. S. 
Published: June 2005

AbstractIn a collaborative effort by 12 centers from Europe and North America, data were assembled from 94 multiplex families with insulin‐dependent diabetes mellitus (IDDM) for analysis of genetic and other factors of possible etiological importance. The dataset contains information on the following genetic markers: HLA‐DRß and ‐DQß restriction fragment length polymorphisms (RFLPs), three RFLPs detected with two probes that map 5′ to the insulin gene, the serologically defined HLA loci, and the immunoglobulin allotypes. Data also were included for auto‐antibodies to insulin and pancreatic islet cells as possible indicators of pathogenesis and for antibodies to certain viruses that have been implicated as “triggering” agents in IDDM. Medical histroy of family members was obtained by means of a uniform questionnaire. Identical copies of the dataset were distributed to anyone wishing to participate in the analysis for the IDDM component of GAW5. The multiplex IDDM family dataset is now available on request for further analysis.
Segregation analysis of two genetic markers in IDDM families under two‐locus models
Authors: Dizier Marie‐Hélène , Clerget‐Darpoux Françoise , Hochez Joëlle 
Published: June 2005

AbstractThe purpose of our study was to examine evidence for the role of a second genetic factor in the susceptibility to IDDM, in addition to that located in the HLA region. To do this, we have studied the joint segregation of HLA and another marker conditional on disease status using the IDDM families of GAW5, under a two‐locus model, one locus in the HLA region, the other close to the other marker. This marker has been, successively, Gm and the DNA polymorphism of the insulin gene 5′ region. The study has been carried out using a segregation analysis method developed to make use of information on the segregation of two markers and the disease in nuclear families. The GAW5 data do not provide evidence for the role of a genetic factor in the Gm or insulin region in the etiology of IDDM.
Statistical properties of the haplotype relative risk
Authors: Ott Jurg 
Published: June 2005

AbstractIn the haplotype relative risk (HRR) statistic (Rubinstein et al.: Human Immunol 3:384 [abstract], 1981), a disease sample is constructed along with its own internal control by comparing those marker alleles passed from the parents to an affected child with the other parental marker alleles not transmitted. Based on the conditional parental genotype distribution given that they have an affected child, statistical properties of the HRR statistic are derived. It is shown that the HRR is different from 1 only when allelic association is present and the recombination fraction is different from 1/2. Transmitted and nontransmitted marker alleles are shown to be statistically independent only in the absence of either allelic association or recombination.
Genetics of IDDM: Evidence for complex inheritance with HLA
Authors: Risch Neil 
Published: June 2005

AbstractAnalysis of the Fifth Genetic Analysis Workshop (GAW5) insulin‐dependent diabetes mellitus (IDDM) data leads to the following conclusions: (1) With a maximum‐likelihood affected sib pair method, there is strong evidence for linkage with HLA and no evidence for linkage with INS, Gm, or Km. (2) Susceptibility as defined by HLA genotypes is very complex. Each DR allele has a unique susceptibility, and DR3 and DR4 haplotype associations for DR 3/4 genotypes are different from those for 3/X and 4/X. (3) Risk is substantially higher in sibships with an affected father compared to those with an affected mother. This excess cannot be attributed to transmission distortion at HLA.
HLA DQβ3.2 identifies subtypes of DR4 + haplotypes permissive for IDDM
Authors: Robinson David M. , Holbeck Susan , Palmer Jerry , Nepom Gerald T. 
Published: June 2005

AbstractThe HLA class II‐related susceptibility to type I insulin‐dependent diabetes mellitus (IDDM) is examined in 94 multiplex families sorted by the presence or absence of a DR4+ haplotype in at least one diabetic family member. The families with DR4+ haplotypes are then sorted by the presence or absence of a DR4‐linked DQβ3.2 allele. Further analysis assumes each multiplex family to represent a single diabetic genetic event and identifies the HLA class II haplotype(s) present in all affected members. The DQβ3.2 allele is present in over 95% of the multiplex families where DR4+ haplotypes segregate with IDDM, implying a major permissive role in determining susceptibility to IDDM.
HLA and insulin gene associations with IDDM
Authors: Thomson G. , Robinson W. P. , Kuhner M. K. , Joe S. , Klitz W. 
Published: June 2005

AbstractThe HLA DR genotype frequencies in insulin‐dependent diabetes mellitus (IDDM) patients and the frequencies of DR alleles transmitted from affected parent to affected child both indicate that the DR3‐associated predisposition is more “recessive” and the DR4‐associated predisposition more “dominant” in inheritance after allowing for the DR3/DR4 synergistic effect. B locus distributions on patient haplotypes indicate that only subsets of both DR3 and DR4 are predisposing Haterogeneity is detected for both the DR3 and DR4 predisposing haplotypes based on DR genotypic class. With appropriate use of the family structure of the data a control population of “unaffected” alleles can be defined. Application of this method confirms the predisposing effect associated with the class 1 allele of the polymorphic region 5′ to the insulin gene.
Age of onset, age at examination, and other covariates in the analysis of family data
Authors: Elston R. C. , George V. T. 
Published: June 2005

AbstractInformation on age of onset can easily be incorporated into regressive logistic models by assuming that age of onset follows a logistic distribution. This is analogous to previously proposed models based on the normal distribution. The two distributions, and hence the two types of models, are very similar. In each case the generalized modulus power transformation can be used as a basis for more flexibly modeling the age of onset distribution.
Familial correlates of risk: Application to the gershon and goldin NIMH pedigree data
Authors: Gilligan Sheila B. , Rice John P. 
Published: June 2005

AbstractSurvival analysis of familial covariates of risk for affective illness demonstrated a significant effect on the proband's diagnosis when affection status included bipolar illness, but not major depressive disorder. A cohort effect was indicated only when broad spectra (including bipolar II and major depressive disorder) of illness were defined. Multifactorial analyses of familial correlations for affective illness evidenced neither sex‐specific correlations nor prevalences. We suggest the examination of risk variables prior to undertaking familial analysis.
A more powerful robust sib‐pair test of linkage for quantitative traits
Authors: Amos C. I. , Elston R. C. , Wilson A. F. , Bailey‐Wilson J. E. , Rao D. C. 
Published: June 2005

AbstractA more powerful robust test for linkage is developed from the methodology of Haseman and Elston [Behav Genet 2(1):3–19, 1972]. This new robust test uses weighted least‐squares (WLS) methods to detect linkage between a quantitative trait and a polymorphic marker. For comparison, the characteristics of a test for linkage that uses known trait genotypes for the parents are also studied. Sample sizes needed to detect linkage, calculated using asymptotic results, are compared for 1) the usual Haseman‐Elston method, 2) the WLS method, and 3) the method that uses parental trait genotype data. The WLS method needs at most twice the number of sib pairs as does the method that used information on the trait genotypes of the parents. The small sample properties of the Haseman‐Elston (H‐E) and WLS tests are investigated by simulation. The power calculations for the H‐E method are found to be accurate. The power of the WLS method is overestimated when fewer than 300 sib pairs are studied, but the WLS method is nonetheless more powerful than the usual H‐E method. In samples of fewer than 300 sib pairs, the WLS test tends to be anticonservative. Treating all sib pairs from sibships of size 3 or 5 as independent does not increase the significance of the tests.
Genetic studies on an Alzheimer Clinic population
Authors: Sadovnick A. D. , Irwin M. E. , Baird P. A. , Beattie B. L. , Conneally P. M. 
Published: June 2005

AbstractAll patients attending the Clinic for Alzheimer Disease and Related Disorders have detailed family histories taken by a geneticist. To date, genetic histories are available for 446 consecutive, unrelated individuals. Of these, 151 (33.9%) are diagnosed as having “probable” (N = 141) or “autopsy‐confirmed” (N = 10) Alzheimer disease according to recognized criteria. This data base represents a relatively unselected population with respect to more than one person in the family having dementia.Seventy‐one of these 151 index cases (47.0%) have a positive family history of dementia, of which 8 (5.3%) may represent the familial (autosomal dominant) form of Alzheimer disease (FAD).Age‐corrected empiric recurrence risks for Alzheimer disease/dementia were calculated for first‐degree relatives of these 151 index cases using the Kaplan‐Meier lifetable method.
Availability of schizophrenic patients and their families for genetic linkage studies: Findings from the Maryland epidemiology sample
Authors: Pulver Ann E. , Bale Sherri J. , Rao D. C. , Vogler G. P. 
Published: June 2005

AbstractIt has been suggested that collections of affected sib pairs, or their nuclear families, may be an efficient method for screening for genetic linkages in schizophrenia. We present the data collected in five years from 15 hospitals in the state of Maryland in an effort to determine if such a collection scheme will be feasible. Probands in our sample were eligible for inclusion in the sample if they were white, were age 16 years or older, and carried a research diagnosis of schizophrenia. Family data are reported for 258 probands. Using the most stringent category of affected (RDC schizophrenia) revealed ten families with two or more affected sibs. The broadest category of affected (any psychotic disorder or psychiatric hospitalization) identified only 36 families with two or more affected sibs. We conclude that, if schizophrenia is a heterogeneous disorder with decreased penetrance, an effort to collect multiplex nuclear families is unlikely to provide enough data to identify genetic linkage. Alternatively, an effort to seek out and collect larger multiplex, multigenerational families rather than a collection of affected sib pairs may be more efficacious.
Phenotypic effects of apolipoprotein structural variation on lipid profiles. IV. Apolipoprotein polymorphisms in a small group of black women from the Healthy Women Study
Authors: Eichner J. E. , Kuller L. H. , Ferrell R. E. , Kamboh M. I. , Vogler G. P. , Rao D. C. 
Published: June 2005

AbstractStructural variation in apolipoprotein E has been shown to influence lipid and lipoprotein concentrations. The purpose of the present study was to investigate several apolipoproteins in a group of Black women from the Healthy Women Study (HWS). HWS is a community‐based prospective study of 541 premenopausal women who are being followed through the menopause to determine the influence of biological, genetic, and psychosocial phenomenon on cardiovascular risk factors. Of the 541 subjects, 48 are Black. Serum from most of these 48 Black women was used to type seven apolipoproteins (APO A‐I, APO A‐II, APO A‐IV, APO C‐II, APO D, APO E, and APO H). Five of these apolipoproteins are polymorphic in Blacks (APO A‐IV, APO C‐II, APO D, APO E and APO H). Only two and three individuals, respectively, were heterozygous at the APO D and APO C‐II loci. APO A‐IV, E, and H exhibited more variation, however, only APO E phenotypes could be used for statistical analyses. Three common phenotypes, APO E 3–2, APO E 3–3, and APO E 4–3, were used in analysis of variance on four quantitative lipid variables. Despite small numbers, the effect of APO E phenotype was apparent. The APO E 3–2 phenotype showed reduced average levels of total cholesterol, apolipoprotein B (APO B) and low‐density lipoprotein cholesterol (LDLC), and the APO E 4–3 phenotype showed increased levels (P ≥ .0497). The APO E 3–3 homozygote was intermediate on all three. Because of small numbers in the cells of APO A‐IV and APO H phenotypes, these were not analyzed with respect to quantitative lipids.
On the role of vitamin D binding globulin in glucose homeostasis: Results from the San Luis Valley diabetes study
Authors: Iyengar Sudha , Hamman Richard F. , Marshall Julie A. , Majumder Partha P. , Ferrell Robert E. , Rao D. C. , Vogler G. P. 
Published: June 2005

AbstractSeveral studies have reported association between noninsulin‐dependent diabetes mellitus and GC, the vitamin D binding protein of human plasma, with the GC 1 allele in significant excess among diabetics. Additionally, there is a considerable body of animal data suggesting that vitamin D has a significant impact on insulin secretion. Examination of the insulin levels in Dogrib Indians showed that the lowest levels of fasting insulin were associated with the GC 1F‐1F genotype. The present study examined levels of glucose, C‐peptide, and insulin at fasting and 1 hr and 2 hr following a 75 g oral glucose challenge, in a population of Hispanic‐Americans and Anglos in the San Luis Valley of southern Colorado. The sample comprised a total of 468 individuals with normal glucose tolerance. Of these, 289 were Anglos and 179 were Hispanic‐Americans. An analysis of covariance was performed to determine the effect of the GC genotypes on mean levels of the primary variables—glucose, C‐peptide, and insulin—and a secondary variable—insulinogenic index adjusting for the covariates age, body mass index (BMI), gender, and ethnicity. The analyses revealed that there is a significant difference in mean levels of glucose at fasting (F value = 2.46; P = 0.033) among the GC genotypes in the sample. Additionally, the differences in mean levels of 1 hr postprandial glucose among the GC genotypes although not significant at a 5% level, were significant at the 10% level. No other significant phenotypic effects were observed. These analyses, are not in concordance the results of an earlier study, where lower fasting insulin was associated with the GC 1F‐1F genotype.