Abstract：
:Case-control studies compare marker-allele distributions in affected and unaffected individuals, and significant results suggest linkage but may simply reflect population structure. For markers with m alleles (m > or = 2), a McNemar-like statistic, I, estimates the level of population association between marker and disease loci. To test for linkage after significant case-control tests, within-family tests are performed. These operate on the contingency table, with i, jth element equal to the number of parents that transmit marker allele Mi and do not transmit marker allele Mi to an affected offspring. The dimension of the table is the number of alleles at the marker locus. Three test statistics have recently been proposed in the literature: Tc compares symmetric pairs of cells (i, j) and (j, i), Tm compares row and column totals for the same marker allele, and a likelihood ratio statistic Tl uses all the cells in the table. In addition, we consider a new statistic, Tmhet, that uses only the heterozygous parents and is approximately chi2 with (m - 1) df. We use a Monte Carlo test to guarantee valid tests and to demonstrate the inferiority of Tc and the equality of Tm and Tl in terms of power. The power of the Tmhet test is close but not always equal to the power of the Tm test. We also show that under the alternative hypothesis of linkage, Tm is approximately noncentral chi2 with (m - 1) df and noncentrality parameter 2NT(1 - 2theta)2I*, when data on single affecteds in NT families are used. If the disease has a low population frequency, then I* is estimated using the case-control statistic I. This offers a basis for choosing sample size, or choosing a marker system.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Kaplan NL,Martin ER,Weir BSsubject
Has Abstractpub_date
1997-03-01 00:00:00pages
691-702issue
3eissn
0002-9297issn
1537-6605journal_volume
60pub_type
杂志文章abstract：:Multiple-synostosis syndrome is an autosomal dominant disorder characterized by progressive symphalangism, carpal/tarsal fusions, deafness, and mild facial dysmorphism. Heterozygosity for functional null mutations in the NOGGIN gene has been shown to be responsible for the disorder. However, in a cohort of six proband...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/503204
更新日期：2006-04-01 00:00:00
abstract：:Data from the Research Roster for Huntington Disease Patients and Families were used to assess the hypothesis that juvenile onset in Huntington disease is determined by an X-linked recessive modifying gene in the affected parent. The observed proportion of affected fathers to affected mothers who had such offspring w...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:The gene for vimentin, an intermediate-filament protein, is growth regulated. We used Southern blot analysis and in situ chromosome hybridization to determine the location of the human vimentin gene. Our results show that there is only one copy of the vimentin gene and that it is located on the short arm of chromosome...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
abstract：:Results are presented on chromosome analyses made on 4,481 embryos or fetuses studied through chorionic villus sampling (CVS) in whom there was no known bias to presence of a chromosome abnormality except advanced parental age. We excluded from the analysis most cases in which mosaicism was diagnosed or in which there...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：:Two of the three class I alcohol dehydrogenase (ADH) genes (ADH2 and ADH3) encode known functional variants that act on alcohol with different efficiencies. Variants at both these genes have been implicated in alcoholism in some populations because allele frequencies differ between alcoholics and controls. Specificall...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302317
更新日期：1999-04-01 00:00:00
abstract：:A cloned 2.2 Eco RI segment of interspersed repetitive DNA was hybridized to genomic DNA from a mentally retarded patient with an interstitial deletion in the long arm of one chromosome 12 (12q-). Under hybridization conditions of high stringency, one prominent 2.2-kilobase (kb) Eco RI fragment demonstrated reduced au...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1984-07-01 00:00:00
abstract：:Two pregnancies at risk for glutaric acidemia were monitored. In one, in which the fetus was not affected, glutaric acid was not detected in the amniotic fluid at amniocentesis (15 weeks) and the glutaryl-CoA dehydrogenase activity of cultured amniotic cells was normal. In the other, a marked elevation of glutaric aci...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1980-09-01 00:00:00
abstract：:Many disorders are associated with altered serum protein concentrations, including malnutrition, cancer, and cardiovascular, kidney, and inflammatory diseases. Although these protein concentrations are highly heritable, relatively little is known about their underlying genetic determinants. Through transethnic meta-an...
journal_title：American journal of human genetics
pub_type： 杂志文章,meta分析
doi：10.1016/j.ajhg.2012.08.021
更新日期：2012-10-05 00:00:00
abstract：:This article provides evidence that selection has been a significant force during the evolution of the human mitochondrial genome. Both gene-by-gene and whole-genome approaches were used here to assess selection in the 560 mitochondrial DNA (mtDNA) coding-region sequences that were used previously for reduced-median-n...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/381505
更新日期：2004-02-01 00:00:00
abstract：:Nijmegen breakage syndrome (NBS; Seemanová II syndrome) and Berlin breakage syndrome (BBS), also known as ataxia-telangiectasia variants, are two clinically indistinguishable autosomal recessive familial cancer syndromes that share with ataxia-telangiectasia similar cellular, immunological, and chromosomal but not cli...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
abstract：:GWAS have been successful in identifying disease susceptibility loci, but it remains a challenge to pinpoint the causal variants in subsequent fine-mapping studies. A conventional fine-mapping effort starts by sequencing dozens of randomly selected samples at susceptibility loci to discover candidate variants, which a...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.04.003
更新日期：2010-05-14 00:00:00
abstract：:The first hypervariable segment of the human mtDNA control region contains a homopolymeric tract of cytosines between nt 16184 and 16193, interrupted at position 16189 by a thymine, according to the Cambridge reference sequence. A variant commonly found in population screening is a T-to-C transition at nt 16189, resul...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:Studies in mouse and chick have shown that the 5' HoxD genes play major roles in the development of the limbs and genitalia. In humans, mutations in HOXD13 cause the dominantly inherited limb malformation synpolydactyly (SPD). Haploinsufficiency for the 5' HOXD genes has recently been proposed to underlie the monodact...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/338921
更新日期：2002-02-01 00:00:00
abstract：:Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental an...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2016.08.003
更新日期：2016-10-06 00:00:00
abstract：:The spinocerebellar ataxia 3 locus (SCA3) for type I autosomal dominant cerebellar ataxia (ADCA type I), a clinically and genetically heterogeneous group of neurodegenerative disorders, has been mapped to chromosome 14q32.1. ADCA type I patients from families segregating SCA3 share clinical features in common with tho...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:Criteria and rules are derived for the most statistically efficient sampling of relatives of affected probands under a simple class of standard genetic models. Results show that the optimal relative type depends on the alternative hypotheses of particular interest. Thus, there is no uniformly optimal strategy, but the...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1981-11-01 00:00:00
abstract：:Cigarette smoke, containing reactive oxygen species, is the most important risk factor for chronic pulmonary emphysema (CPE). Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung. A (GT)n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism and could modul...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302729
更新日期：2000-01-01 00:00:00
abstract：:The lysosomal hydrolase alpha-L-iduronidase (IDUA) is one of the enzymes in the metabolic pathway responsible for the degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate. In humans a deficiency of IDUA leads to the accumulation of glycosaminoglycans, resulting in the lysosomal storage disorder m...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:Ciliopathies are clinical disorders of the primary cilium with widely recognized phenotypic and genetic heterogeneity. In two Arab consanguineous families, we mapped a ciliopathy phenotype that most closely matches Joubert syndrome (hypotonia, developmental delay, typical facies, oculomotor apraxia, polydactyly, and s...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.02.018
更新日期：2019-04-04 00:00:00
abstract：:A high incidence of 46,XX true hermaphroditism exists among southern African blacks. The gonadal distribution and clinical presentation of 38 patients are described. The aim of our study on 11 families with histologically proven XX true hermaphroditism was to determine whether a common genetic or environmental etiolog...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-07-01 00:00:00
abstract：:The practicality and moral value of community review of human genetic research has become a focus of debate. Examples from two Native American communities are used to address four aspects of that debate: (1) the value of community review in larger, geographically dispersed populations; (2) the identification of cultur...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302415
更新日期：1999-06-01 00:00:00
abstract：:The AIMilano apoprotein variant is associated with a marked reduction of high density lipoprotein (HDL) cholesterol levels and with increased triglyceridemia. In spite of the low HDL-cholesterol (HDL-Ch), carriers do not generally show clinical signs of atherosclerosis. The biochemical disorder is linked to a molecula...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:The mtDNA variation of 74 Khoisan-speaking individuals (Kung and Khwe) from Schmidtsdrift, in the Northern Cape Province of South Africa, was examined by high-resolution RFLP analysis and control region (CR) sequencing. The resulting data were combined with published RFLP haplotype and CR sequence data from sub-Sahara...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302848
更新日期：2000-04-01 00:00:00
abstract：:The duplication 17p11.2 syndrome, associated with dup(17)(p11.2p11.2), is a recently recognized syndrome of multiple congenital anomalies and mental retardation and is the first predicted reciprocal microduplication syndrome described--the homologous recombination reciprocal of the Smith-Magenis syndrome (SMS) microde...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/512864
更新日期：2007-04-01 00:00:00
abstract：:We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early dea...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2014.12.013
更新日期：2015-02-05 00:00:00
abstract：:We devised a rapid PCR-based method to screen for an A----G transition at nucleotide 8344 of the human mitochondrial tRNA(Lys) gene, which was recently reported, by Shoffner and co-workers, to be associated with myoclonus epilepsy and ragged-red fibers (MERRF), a maternally transmitted mitochondrial encephalomyopathy ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
abstract：:We describe a log-linear method for analysis of case-parent-triad data, based on maximum likelihood with stratification on parental mating type. The method leads to estimates of association parameters, such as relative risks, for a single allele, and also to likelihood ratio chi2 tests (LRTs) of linkage disequilibrium...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301802
更新日期：1998-04-01 00:00:00
abstract：:In a female infant with dysmorphic features, severe neurological defects, and congenital blindness, a positive urinary Bratton-Marshall test led to identification of a massive excretion of 5-amino-4-imidazolecarboxamide (AICA)-riboside, the dephosphorylated counterpart of AICAR (also termed "ZMP"), an intermediate of ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/421475
更新日期：2004-06-01 00:00:00
abstract：:We report here the characterization of a large Chinese family with maternally transmitted aminoglycoside-induced and nonsyndromic deafness. In the absence of aminoglycosides, some matrilineal relatives in this family exhibited late-onset/progressive deafness, with a wide range of severity and age at onset. Notably, th...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/381133
更新日期：2004-01-01 00:00:00
abstract：:We report an unusual molecular defect in the mitochondrially encoded ND1 subunit of NADH ubiquinone oxidoreductase (complex I) in a patient with mitochondrial myopathy and isolated complex I deficiency. The mutation is an inversion of seven nucleotides within the ND1 gene, which maintains the reading frame. The invers...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302927
更新日期：2000-06-01 00:00:00
