Abstract:
:The definition of haplotype blocks of single-nucleotide polymorphisms (SNPs) has been proposed so that the haplotypes can be used as markers in association studies and to efficiently describe human genetic variation. The International Haplotype Map (HapMap) project to construct a comprehensive catalog of haplotypic variation in humans is underway. However, a number of factors have already been shown to influence the definition of blocks, including the population studied and the sample SNP density. Here, we examine the effect that marker selection has on the definition of blocks and the pattern of haplotypes by using comparable but complementary SNP sets and a number of block definition methods in various genomic regions and populations that were provided by the Encyclopedia of DNA Elements (ENCODE) project. We find that the chosen SNP set has a profound effect on the block-covered sequence and block borders, even at high marker densities. Our results question the very concept of discrete haplotype blocks and the possibility of generalizing block findings from the HapMap project. We comparatively apply the block-free tagging-SNP approach and discuss both the haplotype approach and the tagging-SNP approach as means to efficiently catalog genetic variation.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Nothnagel M,Rohde Kdoi
10.1086/498175subject
Has Abstractpub_date
2005-12-01 00:00:00pages
988-98issue
6eissn
0002-9297issn
1537-6605pii
S0002-9297(07)63383-7journal_volume
77pub_type
杂志文章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::The linkage of polymorphic DNA markers on chromosome 7 to cystic fibrosis (CF) was examined in two pedigrees and a number of smaller nuclear families. The pedigrees are multigenerational and together consist of more than 300 members including 30 affected individuals, while the nuclear families each have two generation...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1986-12-01 00:00:00
abstract::The recent cloning of cDNA encoding the Ca++ release channel (ryanodine receptor) of human sarcoplasmic reticulum has enabled us to use somatic cell hybrids to localize the ryanodine receptor gene (RYR) to the proximal long arm of human chromosome 19. Studies with additional hybrids containing deletions or translocati...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::Keratitis-ichthyosis-deafness syndrome (KID) is a rare ectodermal dysplasia characterized by vascularizing keratitis, profound sensorineural hearing loss (SNHL), and progressive erythrokeratoderma, a clinical triad that indicates a failure in development and differentiation of multiple stratifying epithelia. Here, we ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/339986
更新日期:2002-05-01 00:00:00
abstract::Histochemical assay for ornithine transcarbamylase (OTC) activity in fixed frozen hepatic sections from a woman heterozygous for OTC deficiency revealed two populations of hepatocytes: those with normal activity and those with no activity. This observation, in conjunction with data from previous family studies, confir...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1976-07-01 00:00:00
abstract::Multiminicore disease (MmD) is an autosomal recessive congenital myopathy characterized by the presence of multiple, short core lesions (known as "minicores") in most muscle fibers. MmD is a clinically heterogeneous condition, in which four subgroups have been distinguished. Homozygous RYR1 mutations have been recentl...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/342719
更新日期:2002-10-01 00:00:00
abstract::Alcoholism is a complex disease with both genetic and environmental risk factors. To identify genes that affect the risk for alcoholism, we systematically ascertained and carefully assessed individuals in families with multiple alcoholics. Linkage and association analyses suggested that a region of chromosome 4p conta...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/383283
更新日期:2004-04-01 00:00:00
abstract::Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a metho...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2015.05.005
更新日期:2015-07-02 00:00:00
abstract::Unbalanced Robertsonian translocations are a significant cause of mental retardation and fetal wastage. The majority of homologous rearrangements of chromosome 21 in Down syndrome have been shown to be isochromosomes. Aside from chromosome 21, very little is known about other acrocentric homologous rearrangements. In ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Fibroblast growth factor homologous factors (FHFs) are intracellular proteins which regulate voltage-gated sodium (Nav) channels in the brain and other tissues. FHF dysfunction has been linked to neurological disorders including epilepsy. Here, we describe two sibling pairs and three unrelated males who presented in i...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.10.017
更新日期:2021-01-07 00:00:00
abstract::Bulimia nervosa (BN) is strongly familial, and additive genetic effects appear to contribute substantially to the observed familiality. In turn, behavioral components of BN, such as self-induced vomiting, are reliably measured and heritable. To identify regions of the genome harboring genetic variants conferring susce...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/345801
更新日期:2003-01-01 00:00:00
abstract::Meckel syndrome (MKS) is a rare autosomal recessive lethal condition of unknown origin, characterized by (i) an occipital meningo-encephalocele with (ii) enlarged kidneys, with multicystic dysplasia and fibrotic changes in the portal area of the liver and with ductal proliferation, and (iii) postaxial polydactyly. A g...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302062
更新日期:1998-10-01 00:00:00
abstract::The 7-year IQ scores (WISC) of 116 white and 143 black nonmalformed twins of known zygosity and placental type were ascertained from the NINCDS Collaborative Perinatal Project (NCPP). The type of chorion and zygosity had no significant effect on the mean IQ or among-pair variation. In white monozygotic twins, however,...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1978-07-01 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::Genetic linkage studies have linked congenital contractural arachnodactyly (CCA), a usually mild heritable connective-tissue disorder, to FBN2, the fibrillin gene on chromosome 5. Recently, FBN2 mutations in two patients with CCA have been described. Here we report an A-->T transversion at the -2 position of the conse...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract::The poly(ADP-ribose) polymerase (PADPRP) gene (13q33-qter) depicts a two-allele (A/B) polymorphism. In the noncancer population, the frequency of the B allele is higher among blacks than among whites. Since the incidence of multiple myeloma and prostate and lung cancer is higher in the U.S. black population, we have a...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::We have isolated 68 new RFLP markers on human chromosome 6. Of these, 64 were localized on chromosomal bands by the fluorescent in-situ hybridization (FISH) method, 25 on the short arm and 39 on the long arm. Their distribution was uneven; the markers were localized predominantly in regions of R-positive banding. Elev...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Genome-wide association studies (GWASs) have been successful in detecting variants correlated with phenotypes of clinical interest. However, the power to detect these variants depends on the number of individuals whose phenotypes are collected, and for phenotypes that are difficult to collect, the sample size might be...
journal_title:American journal of human genetics
pub_type: 杂志文章,meta分析
doi:10.1016/j.ajhg.2016.04.013
更新日期:2016-07-07 00:00:00
abstract::Centromeric-mapping methods have been used to investigate the association between altered recombination and meiotic nondisjunction in humans. For trisomies, current methods are based on the genotypes from a trisomic offspring and both parents. Because it is sometimes difficult to obtain samples from both parents and b...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302799
更新日期:2000-03-01 00:00:00
abstract::SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. For SOX6, these processes include, but are not limited to, neurogenesis and skeletogenesis. Variants in half of the SOX genes ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.04.015
更新日期:2020-06-04 00:00:00
abstract::Small low-density lipoprotein (LDL) particles are a genetically influenced coronary disease risk factor. Lipoprotein lipase (LpL) is a rate-limiting enzyme in the formation of LDL particles. The current study examined genetic linkage of LDL particle size to the LpL gene in five families with structural mutations in th...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302234
更新日期:1999-02-01 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::Steroid-resistant nephrotic syndrome (SRNS) is characterized by high-range proteinuria and most often focal and segmental glomerulosclerosis (FSGS). Identification of mutations in genes causing SRNS has improved our understanding of disease mechanisms and highlighted defects in the podocyte, a highly specialized glome...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.12.016
更新日期:2019-02-07 00:00:00
abstract::While genetic causes are known for many syndromes involving developmental anomalies, a large number of individuals with overlapping phenotypes remain undiagnosed. Using exome-sequencing analysis and review of matchmaker databases, we have discovered four de novo missense variants predicted to affect the N-terminal reg...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.06.015
更新日期:2019-08-01 00:00:00
abstract::Ninety extended families having one or more individuals affected with nonsyndromic cleft lip (CL) with or without cleft palate (CL/P) were ascertained in rural West Bengal, India. These families included 138 affected people, 64% of whom had CL alone and 66% of whom were male. Multiple-affected-member ("multiplex") ped...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::When population geneticists wish to determine the genetic consequences of some aspect of mating behavior, it is often necessary to compare observed levels of consanguinity to the level expected when mating is random with respect to the factor being studied. Expectations under random mating are often derived from discr...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1983-09-01 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::New information has been obtained on 30 patients with isolated persistent hypermethioninemia, most of them previously unreported. Biopsies to confirm the presumptive diagnosis of partially deficient activity of ATP: L-methionine S-adenosyltransferase (MAT; E.C.2.5.1.6) in liver were not performed on most of these pati...
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::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::Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a serious and potentially fatal inherited defect in the beta-oxidation of fatty acids. Approximately 80% of patients with MCAD deficiency are homozygous for a single disease-causing mutation (G985). The remaining patients (except for a few cases worldwide) are c...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00