Abstract:
:Quantitative predictions of rates of Down syndrome offspring as a function of maternal serum alpha-fetoprotein (MSAFP) values and of maternal age were reviewed. Comparisons were made of 35-year-equivalent-risk values by maternal age, that is, MSAFP values (at various maternal ages) that predict the risk (of a Down syndrome offspring) equivalent to that of an average 35-year-old woman irrespective of knowledge of MSAFP. This boundary was chosen because MSAFP values that predict a greater risk than this point for younger women or a lower risk for older women are likely in many jurisdictions to alter a decision about amniocentesis that would be reached without knowledge of MSAFP. There were marked differences among available studies in these 35-year-equivalent-risk values for older women. For instance, for age 41, the values among studies vary from 1.5 MoM to 2.1 MoM and the predicted proportion of 41-year-old women likely to be affected clinically by MSAFP determinations by the above criterion is 4.4%-18%, depending on which rate schedule is used. At age 39, the variation is 1.1 to 1.9 MoM or 7.1% to 38%. Possible explanations for the variation include sampling fluctuation. Relatively few data on Down syndrome have been used to calculate the parameters of the gaussian distributions used by the studies reviewed. It is suggested that great caution be used before employing published rate schedules for genetic counseling of older women, at least until sufficient data are collected and the nature of the discrepancies among studies is clarified.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Hook EBsubject
Has Abstractpub_date
1988-08-01 00:00:00pages
160-4issue
2eissn
0002-9297issn
1537-6605journal_volume
43pub_type
杂志文章abstract::Numerous case series have addressed the concern that cancer therapy may damage germ cells, leading to clinical disease in offspring of survivors. None has documented an increased risk. However, the methodological problems of small series make it difficult to draw firm conclusions regarding the potential of cancer trea...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301677
更新日期:1998-01-01 00:00:00
abstract::Allele and genotype frequencies for the highly polymorphic D1S80 locus were determined in a Finnish population sample by using PCR followed by high-resolution PAGE and silver staining, a procedure called the amplified-fragment-length polymorphism (Amp-FLP) technique. In 140 unrelated Finnish individuals 15 alleles and...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::X chromosome inactivation results in the random transcriptional silencing of one of the two X chromosomes early in female development. After random inactivation, certain deleterious X-linked mutations can create a selective disadvantage for cells in which the mutation is on the active X chromosome, leading to X inacti...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302286
更新日期:1999-03-01 00:00:00
abstract::Animal microRNAs (miRNAs) regulate gene expression through base pairing to their targets within the 3' untranslated region (UTR) of protein-coding genes. Single-nucleotide polymorphisms (SNPs) located within such target sites can affect miRNA regulation. We mapped annotated SNPs onto a collection of experimentally sup...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/519979
更新日期:2007-08-01 00:00:00
abstract::Most sporadic cases of retinoblastoma, malignant eye tumor of children, may require the identification of a mutation of the retinoblastoma gene (RB1 gene) for precise genetic counseling. We established a mutation detection system of and screened for the RB1 gene mutation in 24 patients with retinoblastoma--12 bilatera...
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::The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was assessed in 542 sib pairs with MS and in their families. By genotyping 1,978 individuals for HLA-DRB1 alleles, we confirmed the well-established association of MS with HLA-DRB1*15 (HLA-DRB1*1501 and HLA-DRB5*0101), by the transmission/dis...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/323480
更新日期:2001-10-01 00:00:00
abstract::We have shown functional complementation of a genetic deficiency in human cultured cells, using artificial chromosomes derived from cloned human genomic fragments. A 404-kb human-artificial-chromosome (HAC) vector, consisting of 220 kb of alphoid DNA from the centromere of chromosome 17, human telomeres, and the hypox...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/321977
更新日期:2001-08-01 00:00:00
abstract::Premature ovarian failure (POF) is characterized by elevated gonadotropins and amenorrhea in women aged <40 years. In a Lebanese family with five sisters who received the diagnosis of POF, we established linkage to the long arm of the X chromosome (between Xq21.1 and Xq21.3.3), using whole-genome SNP typing and homozy...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/505406
更新日期:2006-07-01 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::The tRNA synthetases catalyze the first step of protein synthesis and have increasingly been studied for their nuclear and extra-cellular ex-translational activities. Human genetic conditions such as Charcot-Marie-Tooth have been attributed to dominant gain-of-function mutations in some tRNA synthetases. Unlike domina...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.06.006
更新日期:2018-07-05 00:00:00
abstract::The segregation of COL1A1 and COL1A2, the two genes which encode the chains of type I collagen, was analyzed in 38 dominant osteogenesis imperfecta (OI) pedigrees by using polymorphic markers within or close to the genes. This was done in order to estimate the consistency of linkage of OI genes to these two loci. None...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::A nonparametric statistical methodology is used for the analysis of biochemical frequency data observed on a series of nine Jewish and six non-Jewish populations. Two categories of statistics are used: heterogeneity indices and various distance measures with respect to a standard. The latter are more discriminating in...
journal_title:American journal of human genetics
pub_type: 历史文章,杂志文章
doi:
更新日期:1979-05-01 00:00:00
abstract::Van der Woude syndrome (VWS) is an autosomal dominant disorder in which affected individuals have one or more of the following manifestations: cleft lip, cleft palate, hypodontia, or paramedian lower-lip pits. VWS is a well-characterized example of a single-gene abnormality that disturbs normal craniofacial morphogene...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::An expanded G4C2 repeat in C9orf72 represents the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the lower limit for pathological expansions is unknown (the suggested cutoff is 30 repeats). It has been proposed that the expansion might have...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2015.04.016
更新日期:2015-06-04 00:00:00
abstract::In recent years, many genomewide screens have been performed, to identify novel loci predisposing to various complex diseases. Often, only a portion of the collected clinical data from the study subjects is used in the actual analysis of the trait, and much of the phenotypic data is ignored. With proper consent, these...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/321286
更新日期:2001-07-01 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::In a study of 908 males from Europe, northern Africa, and western Asia, the variation of four Y-linked dinucleotide microsatellites was analyzed within three "frames" that are defined by mutations that are nonrecurrent, or nearly so. The rapid generation and extinction of new dinucleotide length variants causes the ha...
journal_title:American journal of human genetics
pub_type: 杂志文章,多中心研究
doi:10.1086/301999
更新日期:1998-09-01 00:00:00
abstract::Myotubular myopathy is a severe congenital disease inherited as an X-linked trait (MTM1; McKusick 31040). It has been mapped to the long arm of chromosome X, to the Xq27-28 region. Significant linkage has subsequently been established for the linkage group comprised of DXS304, DXS15, DXS52, and F8C in several studies....
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-07-01 00:00:00
abstract::A gene for Holt-Oram syndrome (HOS) has been previously mapped to chromosome 12q2 and designated HOS1. We have identified a HOS patient with a de novo chromosomal rearrangement involving 12q. Detailed cytogenetic analysis of this case reveals three breaks on 12q, and two of these are within the HOS1 interval. By using...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-12-01 00:00:00
abstract::Some genes that affect development and behavior in mammals are known to be imprinted; and > or = 1% of all mammalian genes are imprinted. Hence, incorporating an imprinting parameter into linkage analysis may increase the power to detect linkage for these traits. Here we propose theoretical justifications for a recent...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/338931
更新日期:2002-03-01 00:00:00
abstract::Beckwith-Wiedeman syndrome (BWS) and Klippel-Trenaunay-Weber syndrome (KTWS) are different human disorders characterized, among other features, by tissue overgrowth. Deregulation of one or more imprinted genes located at chromosome 11p15.5, of which insulin-like growth factor 2 (IGF2) is the most likely candidate, is ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302811
更新日期:2000-03-01 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::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
abstract::Usher syndrome type IIa is an autosomal recessive disorder characterized by mild-to-severe hearing loss and progressive visual loss due to retinitis pigmentosa. The mutation that most commonly causes Usher syndrome type IIa is a 1-bp deletion, described as "2299delG," in the USH2A gene. The mutation has been identifie...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/321269
更新日期:2001-07-01 00:00:00
abstract::Cranial neural crest (CNC) is a multipotent migratory cell population that gives rise to most of the craniofacial bones. An intricate network mediates CNC formation, epithelial-mesenchymal transition, migration along distinct paths, and differentiation. Errors in these processes lead to craniofacial abnormalities, inc...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.01.003
更新日期:2011-02-11 00:00:00
abstract::Autosomal dominant familial exudative vitreoretinopathy (adFEVR) is a hereditary disorder characterized by the incomplete vascularization of the peripheral retina. The primary biochemical defect in adFEVR is unknown. The adFEVR locus has tentatively been assigned to 11q by linkage studies. We report the results of an ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::Familial Mediterranean fever (FMF) is a recessively inherited disorder that is common in patients of Armenian ancestry. To date, its diagnosis, which can be made only retrospectively, is one of exclusion, based entirely on nonspecific clinical signs that result from serosal inflammation and that may lead to unnecessar...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302459
更新日期:1999-07-01 00:00:00
abstract::Eighty unrelated individuals with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) were found to have deletions in the major deletion-rich region of the DMD locus. This region includes the last five exons detected by cDNA5b-7, all exons detected by cDNA8, and the first two exons detected by cDNA9. ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract::Revertant mosaicism is an infrequently observed phenomenon caused by spontaneous correction of a pathogenic allele. We have observed such reversions caused by mitotic recombination of mutant TERC (telomerase RNA component) alleles in six patients from four families affected by dyskeratosis congenita (DC). DC is a mult...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.01.004
更新日期:2012-03-09 00:00:00
abstract::The Hawaii Family Study of Cognition provided an opportunity to investigate the frequency and implications of non-agreement, or mismatches, between observed and expected genetic marker phenotypes of husbands, wives, and children. Mismatch data from 68 families in which one or both spouses were known not to be a biolog...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1980-07-01 00:00:00