Abstract:
:The effects of reproductive compensation on an X-linked recessive lethal are examined. Complete compensation without regard to the sex of the offspring increases the incidence of female carriers by a factor of 1.5, and of affected males by 1.33. However, if families reproduce until they have a healthy male offspring, the incidence of the X-linked lethal can be increased two or three orders of magnitude. Even only 1% of the population reproducing until a male is born can inflate the incidence of the disease by an order of magnitude, provided this pattern of family planning is culturally inherited. Similarly, reproducing until there is at least one child of each sex increases the incidence of an X-linked lethal. The impact of these types of sex-biased family planning on the fraction of new mutants among affect males is discussed.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Templeton AR,Yokoyama Ssubject
Has Abstractpub_date
1980-07-01 00:00:00pages
575-81issue
4eissn
0002-9297issn
1537-6605journal_volume
32pub_type
杂志文章abstract::Mastocytosis is a rare myeloid neoplasm characterized by uncontrolled expansion of mast cells, driven in >80% of affected individuals by acquisition of the KIT D816V mutation. To explore the hypothesis that inherited variation predisposes to mastocytosis, we performed a two-stage genome-wide association study, analyzi...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.12.007
更新日期:2021-01-04 00:00:00
abstract::X-linked retinitis pigmentosa (XLRP) is a clinically and genetically heterogeneous degenerative disease of the retina. At least five loci have been mapped for XLRP; of these, RP2 and RP3 account for 10%-20% and 70%-90% of genetically identifiable disease, respectively. However, mutations in the respective genes, RP2 a...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/340848
更新日期:2002-06-01 00:00:00
abstract::Linkage analyses were performed in 11 families with X-linked Menkes disease. In each family more than one affected patient had been diagnosed. Forty informative meioses were tested using 11 polymorphic DNA markers. From two-point linkage analyses high lod scores are seen for DXS146 (pTAK-8; maximal lod score 3.16 at r...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::Myoclonus-dystonia (M-D) is a movement disorder characterized by rapid muscle contractions and sustained twisting and repetitive movements and has recently been associated with mutations in the epsilon-sarcoglycan gene (SGCE). The mode of inheritance is autosomal dominant with reduced penetrance upon maternal transmis...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/344531
更新日期:2002-12-01 00:00:00
abstract::The PCR technique was used to analyze the DXYS17 locus in the pseudoautosomal region of the X and the Y chromosomes. Analysis on an automated DNA sequencer allowed for sensitive and highly accurate typing of 16 different alleles with a size between 480 and 1,100 bp. Two DXYS17 alleles migrated with the same size on ag...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract::The critical importance of cytoskeletal function for correct neuronal migration during development of the cerebral cortex has been underscored by the identities of germline mutations underlying a number of human neurodevelopmental disorders. The proteins affected include TUBA1A, a major alpha-tubulin isoform, and micr...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2009.10.007
更新日期:2009-11-01 00:00:00
abstract::A proband, clinically thought to have trisomy 10p, was found to have an inverted duplication of 10p [46, XY, inv dup(10)(qter----p15.3::p15.3----p 11.1:)]. The phenotypic findings and cytogenetic observations were supported by relevant biochemical studies. The activity of phosphofructokinase (platelet-type; PFKP), pre...
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::Genetic association studies of common disease often rely on linkage disequilibrium (LD) along the human genome and in the population under study. Although understanding the characteristics of this correlation has been the focus of many large-scale surveys (culminating in genomewide haplotype maps), the results of diff...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/502803
更新日期:2006-04-01 00:00:00
abstract::Phenotypes are rarely consistent across genetic backgrounds and environments, but instead vary in many ways depending on allelic variants, unlinked genes, epigenetic factors, and environmental exposures. In the extreme, individuals carrying the same causal DNA sequence variant but on different backgrounds can be class...
journal_title:American journal of human genetics
pub_type: 杂志文章,评审
doi:10.1016/j.ajhg.2017.06.004
更新日期:2017-08-03 00:00:00
abstract::Genetic risks are usually computed under the assumption that genetic parameters, such as the recombination fraction, are known without error. Uncertainty in the estimates of these parameters must translate into uncertainty regarding the risk. To allow for uncertainties in parameter values, one may employ Bayesian tech...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-05-01 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::We present a systematic review of pleiotropy among SNPs and genes reported to show genome-wide association with common complex diseases and traits. We find abundant evidence of pleiotropy; 233 (16.9%) genes and 77 (4.6%) SNPs show pleiotropic effects. SNP pleiotropic status was associated with gene location (p = 0.024...
journal_title:American journal of human genetics
pub_type: 杂志文章,评审
doi:10.1016/j.ajhg.2011.10.004
更新日期:2011-11-11 00:00:00
abstract::We used whole-exome sequencing to study three individuals with a distinct condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, cleft palate, and facial dysmorphism. Affected individuals carried homozygous missense mutations in IMPAD1, the gene coding for gPAPP, ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.04.002
更新日期:2011-05-13 00:00:00
abstract::Galactosemia is an autosomal recessive disorder of human galactose metabolism caused by deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT). The molecular basis of this disorder is at present not well understood. We report here two missense mutations which result in low or undetectable enzymatic a...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::Identification and description of genetic variation underlying disease susceptibility, efficacy, and adverse reactions to drugs remains a difficult problem. One of the important steps in the analysis of variation in a candidate region is the characterization of linkage disequilibrium (LD). In a region of genetic assoc...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/503710
更新日期:2006-05-01 00:00:00
abstract::Isolated complex I deficiency is a common biochemical phenotype observed in pediatric mitochondrial disease and often arises as a consequence of pathogenic variants affecting one of the ∼65 genes encoding the complex I structural subunits or assembly factors. Such genetic heterogeneity means that application of next-g...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.08.013
更新日期:2018-10-04 00:00:00
abstract::Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that is phenotypically similar to but genetically distinct from Marfan syndrome. Genetic-linkage analysis has implicated the fibrillin-2 gene (FBN2) as the CCA locus. Mutation analysis of two isolated CCA patients revealed missense mutation...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/515472
更新日期:1997-06-01 00:00:00
abstract::Genes on chromosomes 17q and 18q have been shown to code for putative tumor suppressors. By a combination of allele-loss studies on sporadic ovarian carcinomas and linkage analysis on a breast/ovarian cancer family, we have investigated the involvement of such genes in these diseases. Allele loss occurred in sporadic ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::The genetically inactive, late-replicating human female X chromosome can be effectively distinguished from its more active, earlier-replicating homologue, when cells are grown according to the appropriate BrdU-33258 Hoechst protocol. Results obtained from a fluorescence analysis of DNA replication in X chromosomes are...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1976-05-01 00:00:00
abstract::The gene responsible for Krabbe disease, an autosomal recessive disorder caused by deficiency of galactocerebrosidase (GALC), was localized by multipoint linkage analysis on chromosome 14. Eight mapped dinucleotide repeat polymorphisms were tested for linkage to GALC. Two-point linkage analysis demonstrated close link...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::Thyroid-stimulating hormone (TSH) controls thyroid growth and hormone secretion through binding to its G protein-coupled receptor (TSHR) and production of cyclic AMP (cAMP). Serum TSH is a sensitive indicator of thyroid function, and overt abnormalities in thyroid function lead to common endocrine disorders affecting ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.04.019
更新日期:2008-06-01 00:00:00
abstract::Robinow syndrome is a rare congenital disorder characterized by mesomelic limb shortening, genital hypoplasia, and distinctive facial features. Recent reports have identified, in individuals with dominant Robinow syndrome, a specific type of variant characterized by being uniformly located in the penultimate exon of D...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.01.005
更新日期:2016-03-03 00:00:00
abstract::Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in approximately 25% of probands. We report identification of de novo nonsen...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/510020
更新日期:2006-12-01 00:00:00
abstract::Distal hereditary motor neuropathies comprise a clinically and genetically heterogeneous group of disorders. We recently mapped an X-linked form of this condition to chromosome Xq13.1-q21 in two large unrelated families. The region of genetic linkage included ATP7A, which encodes a copper-transporting P-type ATPase mu...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2010.01.027
更新日期:2010-03-12 00:00:00
abstract::Genomic rearrangements involving the peripheral myelin protein gene (PMP22) in human chromosome 17p12 are associated with neuropathy: duplications cause Charcot-Marie-Tooth disease type 1A (CMT1A), whereas deletions lead to hereditary neuropathy with liability to pressure palsies (HNPP). Our previous studies showed th...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2010.05.001
更新日期:2010-06-11 00:00:00
abstract::Methylmalonyl CoA mutase (MCM) catalyzes an essential step in the degradation of several branch-chain amino acids and odd-chain fatty acids. Deficiency of this apoenzyme causes the mut form of methylmalonic acidemia, an often fatal disorder of organic acid metabolism. An MCM cDNA has recently been obtained from human ...
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::Recent studies have suggested that a significant fraction of the human genome is contained in blocks of strong linkage disequilibrium, ranging from ~5 to >100 kb in length, and that within these blocks a few common haplotypes may account for >90% of the observed haplotypes. Furthermore, previous studies have suggested...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/382227
更新日期:2004-04-01 00:00:00
abstract::Down syndrome (DS) is the most common cause of mental retardation. Many neural phenotypes are shared between DS individuals and DS mouse models; however, the common underlying molecular pathogenetic mechanisms remain unclear. Using a transchromosomic model of DS, we show that a 30%-60% reduced expression of Nrsf/Rest ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.08.012
更新日期:2008-09-01 00:00:00
abstract::It is unclear at present whether specific mtDNA point mutations accumulate during normal human aging. In order to address this question, we used quantitative PCR of total DNA isolated from skeletal muscle from normal individuals of various ages to search for the presence and amount of spontaneous mtDNA point mutations...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::The mode of inheritance of bipolar affective disorder (BPAD) appears complex, and non-Mendelian models of inheritance have been postulated. Two non-Mendelian phenomena, genomic imprinting and mitochondrial inheritance, may contribute to the complex inheritance pattern seen in BPAD. Both imprinting and mitochondrial in...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00