Abstract：
:Studies have demonstrated that natural variation in the expression level of genes at baseline is extensive, and the determinants of this variation can be mapped by a genetic-linkage approach. In this study, we used lymphoblastoid cells to explore the variation in radiation-induced transcriptional changes. We found that, among normal individuals, there is extensive variation in transcriptional response to radiation exposure. By studying monozygotic twins, we demonstrated that there is evidence of a heritable component to this variation. The postradiation variation in the expression level of several genes, including the ferredoxin reductase gene (FDXR) and the cyclin-dependent kinase inhibitor 1A gene (CDKN1A), is significantly greater (P<.001) among twin pairs than within twin pairs. The induction of FDXR by radiation showed a bimodal distribution. Our findings have important implications for understanding the genetic basis of radiation response, which has remained largely unknown due to the lack of family material needed for genetic studies. Our approach, which uses expression phenotypes in cell lines, allows us to expose cells from family members to radiation. Similar study design can be applied to dissect the genetic basis of other complex human traits.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Correa CR,Cheung VGdoi
10.1086/425221subject
Has Abstractpub_date
2004-11-01 00:00:00pages
885-90issue
5eissn
0002-9297issn
1537-6605pii
S0002-9297(07)63794-Xjournal_volume
75pub_type
杂志文章abstract：:The affected sib-pair method has been used to investigate the mode of inheritance, and to estimate the "disease" allele frequency, for a number of HLA-associated diseases. One of the assumptions of the original sib-pair method is that the disease confers no selective disadvantage on affected individuals. This is obvio...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1984-03-01 00:00:00
abstract：:Subcutaneous adipose tissue stores excess lipids and maintains energy balance. We performed expression quantitative trait locus (eQTL) analyses by using abdominal subcutaneous adipose tissue of 770 extensively phenotyped participants of the METSIM study. We identified cis-eQTLs for 12,400 genes at a 1% false-discovery...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2017.01.027
更新日期：2017-03-02 00:00:00
abstract：:A wide variety of mutations in the parkin gene, including exon deletions and duplications, as well as point mutations, result in autosomal recessive early-onset parkinsonism. Interestingly, several of these anomalies were found repeatedly in unrelated patients and may therefore result from recurrent, de novo mutationa...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/318791
更新日期：2001-03-01 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：: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：:Serum and leukocyte hexosaminidase profiles (total activity and percent heat-labile activity levels) in obligate Sandhoff disease (SHD) heterozygotes differ from those of obligate Tay-Sachs disease (TSD) heterozygotes and noncarrier individuals. We have developed a procedure to identify, with 95% sensitivity, carriers...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1985-09-01 00:00:00
abstract：:X-linked ichthyosis (XLI) is an inborn error of metabolism caused by steroid sulfatase (STS) deficiency. In more than 80% of XLI patients the enzyme deficiency is due to large deletions involving the entire STS gene and flanking sequences. However, some patients with the classical XLI phenotype and complete STS defici...
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：:Regions on chromosomes 7 and 19 were recently reported to contain susceptibility loci that regulate tumor aggressiveness of prostate cancer. To confirm these findings, we analyzed genome scan data from 161 pedigrees affected with prostate cancer. Using the Gleason score as a quantitative measure of tumor aggressivenes...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/368230
更新日期：2003-03-01 00:00:00
abstract：:The Coffin-Lowry syndrome (CLS) is an X-linked inherited disease of unknown pathogenesis characterized by severe mental retardation, typical facial and digital anomalies, and progressive skeletal deformations. Our previous linkage analysis, based on four pedigrees with the disease, suggested a localization for the CLS...
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：:The first component of the mitochondrial electron-transport chain is especially complex, consisting of 19 nuclear and seven mitochondrion-encoded subunits. Accordingly, a wide range of clinical manifestations are produced by the various mutations occurring in human populations. In this study, we analyze the subunit st...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-06-01 00:00:00
abstract：:Prenatal hemoglobinopathy screening was chosen as a model system for the study of patient receptivity to unsolicited genetic information. Providers of prenatal care in Rochester, NY, were offered free testing of all their prenatal patients and genetic counseling of women found positive. The 18,907 prenatal samples tes...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:Linkage markers at or close to the genes encoding the three major fibrillar collagens were used to analyze the segregation of these loci in six pedigrees with dominantly inherited Marfan syndrome. Four pedigrees were discordant at one of the Type I collagen loci (COL1A2), and, of these, two were discordant at the othe...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed behavioral disorder in childhood and likely represents an extreme of normal behavior. ADHD significantly impacts learning in school-age children and leads to impaired functioning throughout the life span. There is strong evidence for a gene...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/342732
更新日期：2002-10-01 00:00:00
abstract：:D1S1, a human anonymous DNA clone originally called lambda Ch4A-H3 or lambda H3, was mapped by two other laboratories to human chromosome 1p36 by in situ hybridization but its localization was not confirmed using a different mapping method. We used a panel of human-hamster somatic cell hybrids to show that there are c...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-04-01 00:00:00
abstract：:The highly polymorphic locus D2S3 is revealed by three single-copy probes from cosmid C1-5. These probes, 1-30, 1-32, and 2-96, collectively reveal seven restriction fragment length polymorphisms. Fifty-three of 56 unrelated individuals (93%) were heterozygous at one or more of the seven loci, making the compound locu...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：:Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.10.002
更新日期：2012-11-02 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 hereditary spastic paraplegias (HSPs) are genetically heterogeneous disorders characterized by progressive lower-extremity weakness and spasticity. The molecular pathogenesis is poorly understood. We report discovery of a dominant negative mutation in the NIPA1 gene in a kindred with autosomal dominant HSP (ADHSP)...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/378817
更新日期：2003-10-01 00:00:00
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：:Joubert syndrome and related disorders (JSRD) are primarily autosomal-recessive conditions characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation. Variable features include retinal dystrophy, cystic kidney disease, and liver fibrosis. JSRD ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2008.10.002
更新日期：2008-11-01 00:00:00
abstract：:Bloom syndrome, caused by biallelic mutations in BLM, is characterized by prenatal-onset growth deficiency, short stature, an erythematous photosensitive malar rash, and increased cancer predisposition. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges (SCEs) on cytogenetic tes...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.07.001
更新日期：2018-08-02 00:00:00
abstract：:Lysinuric protein intolerance (LPI) is an autosomal recessive disease characterized by defective transport of cationic amino acids and by hyperammonemia. Linkage analysis in 20 Finnish LPI families assigned the LPI gene locus to the proximal long arm of chromosome 14. Recombinations placed the locus between framework ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/515457
更新日期：1997-06-01 00:00:00
abstract：:We present a novel method for simultaneous genotype calling and haplotype-phase inference. Our method employs the computationally efficient BEAGLE haplotype-frequency model, which can be applied to large-scale studies with millions of markers and thousands of samples. We compare genotype calls made with our method to ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2009.11.004
更新日期：2009-12-01 00:00:00
abstract：:Deletions of the long arm of chromosome 18 occur in approximately 1 in 10,000 live births. Congenital aural atresia (CAA), or narrow external auditory canals, occurs in approximately 66% of all patients who have a terminal deletion 18q. The present report describes a series of 20 patients with CAA, of whom 18 had micr...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/375695
更新日期：2003-06-01 00:00:00
abstract：:Mitochondrial DNA (mtDNA) polymorphisms were detected using 13 restriction enzymes on the total DNA obtained from blood samples of five Asian populations: Japanese and Ainu of northern Japan, Korean, Negrito (Aeta) of the Philippines, and Vedda of Sri Lanka. Of a total of 28 restriction-enzyme morphs detected, eight h...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:Both the optimal marker density for genome scans in case-control association studies and the appropriate study design for the testing of candidate genes depend on the genomic pattern of linkage disequilibrium (LD). In this study, we provide the first conclusive demonstration that the diverse demographic histories of h...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/303083
更新日期：2000-10-01 00:00:00
abstract：:Multiple morphological abnormalities of the sperm flagellum (MMAF) is a severe form of male infertility defined by the presence of a mosaic of anomalies, including short, bent, curled, thick, or absent flagella, resulting from a severe disorganization of the axoneme and of the peri-axonemal structures. Mutations in DN...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.07.014
更新日期：2018-09-06 00:00:00
abstract：:A patients with seizures, Von Willebrand disease, and symptoms of Turner syndrome was a chromosomal mosaic. In blood culture (1974), 56% of the cells were 45, X 33% 46, XXp+ and 11% 47,XXp + Xp +; in the skin, no cells with 47 chromosomes were found. Presumably the Xp + chromosome arose through a break in the Q-banded...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1977-01-01 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：:Recently, Schork et al. found that two-trait-locus, two-marker-locus (parametric) linkage analysis can provide substantially more linkage information than can standard one-trait-locus, one-marker-locus methods. However, because of the increased burden of computation, Schork et al. do not expect that their approach wil...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
