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 treatments to damage the health of future offspring. We conducted a large interview study of adult survivors of childhood cancer treated before 1976. Genetic disease occurred in 3.4% of 2,198 offspring of survivors, compared with 3.1% of 4,544 offspring of controls (P=.33; not significant); there were no statistically significant differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with survivors not so treated showed no association with sporadic genetic disease (P=.49). The present study provides reassurance that cancer treatment using older protocols does not carry a large risk for genetic disease in offspring conceived many years after treatment. With 80% power to detect an increase as small as 40% in the rate of genetic disease in offspring, this study did not do so. However, we cannot rule out the possibility that new therapeutic agents or specific combinations of agents at high doses may damage germ cells.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Byrne J,Rasmussen SA,Steinhorn SC,Connelly RR,Myers MH,Lynch CF,Flannery J,Austin DF,Holmes FF,Holmes GE,Strong LC,Mulvihill JJdoi
10.1086/301677subject
Has Abstractpub_date
1998-01-01 00:00:00pages
45-52issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(07)60121-9journal_volume
62pub_type
杂志文章abstract：:The cellular mechanism for the expression of the fragile site at Xq28 is unknown. We tested the effect of 5-azacytidine and methionine on fragile X expression in lymphocytes and lymphoblastoid cells in an attempt to determine if DNA methylation was involved. We were unable to demonstrate a consistent dosage effect of ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：:Gilles de la Tourette syndrome (GTS) is characterized by multiple motor and phonic tics and high comorbidity rates with other neurobehavioral disorders. It is hypothesized that frontal-subcortical pathways and a complex genetic background are involved in the etiopathogenesis of the disorder. The genetic basis of GTS r...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/424389
更新日期：2004-10-01 00:00:00
abstract：:We recently identified a mutation in the I-kappa B kinase associated protein (IKBKAP) gene as the major cause of familial dysautonomia (FD), a recessive sensory and autonomic neuropathy. This alteration, located at base pair 6 of the intron 20 donor splice site, is present on >99.5% of FD chromosomes and results in ti...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/368263
更新日期：2003-03-01 00:00:00
abstract：:Fibroblast cultures from 12 unrelated patients with classical Menkes disease were analyzed for mutations in the MNK gene, by reverse transcription-PCR (RT-PCR) and chemical cleavage mismatch detection. Mutations were observed in 10 patients, and in each case a different mutation was present. All of the mutations would...
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：:Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) are axonal peripheral neuropathies inherited in an autosomal dominant fashion. Our previous genetic and physical mapping efforts localized the responsible gene(s) to a well-defined region on human chromosome 7p. Here, we rep...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/375039
更新日期：2003-05-01 00:00:00
abstract：:Three new cases of Sandhoff disease are reported. One infant was the second affected child in a large family. The parents, who were cousins, were part of a large kindred from an isolated community in northern Saskatchewan. We assayed total and heat-stable hexosaminidases in 38 other members of the kindred and found tw...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
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：:Attention-deficit hyperactivity disorder (ADHD) affects approximately 3%-5% of children in the United States. In the current psychiatric nomenclature, ADHD comprises three subtypes: inattentive, hyperactive-impulsive, and combined. In this study, we used four analytic strategies to examine the association and linkage ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302132
更新日期：1998-12-01 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：: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 di...
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：:Aberrant gene expression underlies many human diseases. RNA polymerase II (Pol II) pausing is a key regulatory step in transcription. Here, we mapped the locations of RNA Pol II in normal human cells and found that RNA Pol II pauses in a consistent manner across individuals and cell types. At more than 1,000 genes inc...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.08.003
更新日期：2019-10-03 00:00:00
abstract：:gamma-Aminobutyric acid transaminase (GABAT, E.C.2.6.I.19) was phenotyped by starch-gel electrophoresis in post-mortem liver samples from 650 unrelated subjects of either sex, comprising 289 Chinese, 177 Indians, 140 Malays, and 44 from other racial groups from Southeast Asia. The estimated gene frequencies of GABAT1 ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1985-03-01 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：:To investigate the transmission of Tourette syndrome (TS) and associated disorders within families, complex segregation analysis was performed on family study data obtained from 53 independently ascertained children and adolescents with TS and their 154 first-degree relatives. The results suggest that the susceptibili...
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：:DNA methylation is assumed to be complementary on both alleles across the genome, although there are exceptions, notably in regions subject to genomic imprinting. We present a genome-wide survey of the degree of allelic skewing of DNA methylation with the aim of identifying previously unreported differentially methyla...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.01.014
更新日期：2010-02-12 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：:The power of structured exploratory data analysis (SEDA) to discriminate among major genic, polygenic, and nongenetic determination of phenotypes was investigated using computer simulation. Three classes of SEDA indices (the major gene index, the offspring between parents function, and the midparent-child correlation ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:Allan-Herndon-Dudley syndrome was among the first of the X-linked mental retardation syndromes to be described (in 1944) and among the first to be regionally mapped on the X chromosome (in 1990). Six large families with the syndrome have been identified, and linkage studies have placed the gene locus in Xq13.2. Mutati...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/431313
更新日期：2005-07-01 00:00:00
abstract：:Mutation scanning and direct DNA sequencing of all 50 exons of ABCR were completed for 150 families segregating recessive Stargardt disease (STGD1). ABCR variations were identified in 173 (57%) disease chromosomes, the majority of which represent missense amino acid substitutions. These ABCR variants were not found in...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302251
更新日期：1999-02-01 00:00:00
abstract：:Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohor...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.05.015
更新日期：2019-07-03 00:00:00
abstract：:Two new morphs (F and G) detected by the centromeric alpha satellite probe p alpha 10RP8 and D10Z1 in HinfI digests are linked to the PstI polymorphisms of D10Z1, confirming their chromosome 10 location. The F and G morphs were in strong linkage disequilibrium with each other but were in weak linkage disequilibrium wi...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:Restless legs syndrome (RLS) is a common neurological disorder that affects 5%-12% of all whites. To genetically dissect this complex disease, we characterized 15 large and extended multiplex pedigrees, consisting of 453 subjects (134 affected with RLS). A familial aggregation analysis was performed, and SAGE FCOR was...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/420772
更新日期：2004-05-01 00:00:00
abstract：:Congenital limb malformations rank behind only congenital heart disease as the most common birth defects observed in infants. Finding genes that cause defects in human limb patterning should be straightforward but has been limited, in part, by the bewildering spectrum of phenotypes, which are difficult to separate int...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301687
更新日期：1998-01-01 00:00:00
abstract：:Patients with a strong family history of breast cancer are often counseled to receive genetic screening for BRCA1 and BRCA2 mutations, the strongest known predictors of breast cancer. A major limitation of genetic testing is the number of inconclusive results due to unclassified BRCA1 and BRCA2 sequence variants. Many...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/342192
更新日期：2002-09-01 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：:To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the dis...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：:The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset < 60 years), and late-onset families. A genetic association was observed between apolipo...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-04-01 00:00:00
abstract：:Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified. In the current investigation, 25 previously undescribed mut...
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：: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：:Hypotrichosis simplex (HS) comprises a group of hereditary isolated alopecias that are characterized by a diffuse and progressive loss of hair starting in childhood and shows a wide phenotypic variability. We mapped an autosomal-dominant form of HS to chromosome 1q31.3-1q41 in a Spanish family. By direct sequencing, w...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.10.022
更新日期：2013-01-10 00:00:00
