Abstract：
:Cells derived from patients with the cancer-prone inherited disorder ataxia-telangiectasia (A-T) show an abnormal response to ionizing radiation-induced DNA damage, such as an increased cell killing and a diminished inhibition of DNA synthesis. The enhanced killing of A-T (group D) cells by X-rays can be corrected by multiple cDNAs, mapping to different chromosomes (6, 11, 17, and 18). In order to examine whether genes located on these chromosomes complement AT-D cells, normal neo-tagged chromosomes 6, 11, 17, and 18 were introduced into AT-D cells by microcell-mediated chromosome transfer. However, correction of the enhanced killing of AT-D cells by X-rays could only be achieved by chromosome 11 and by none of the other chromosomes tested. The enhanced killing of A-T (complementation group C) cells was also corrected by chromosome 11. Usually, but not in all microcell hybrid clones, chromosome 11 also corrected the radioresistant DNA synthesis (RDS) phenotype of AT-D and AT-C cells. These results (i) confirm findings by others suggesting assignment of the ATD and ATC genes to chromosome 11, (ii) demonstrate that several genes can modify the cellular radiation response when they are taken out of their normal genomic context and/or control, and (iii) indicate that the RDS phenotype and the enhanced cell killing in A-T are independent pleiotropic features resulting from the primary mutations in A-T. Also, our findings underscore that, in establishing cDNAs as candidate genes for A-T, microcell-mediated chromosome transfer studies are needed to exclude nonspecific correcting effects of these candidate cDNA genes.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Jongmans W,Verhaegh GW,Jaspers NG,Oshimura M,Stanbridge EJ,Lohman PH,Zdzienicka MZsubject
Has Abstractpub_date
1995-02-01 00:00:00pages
438-43issue
2eissn
0002-9297issn
1537-6605journal_volume
56pub_type
杂志文章abstract：:The distal portion of the short arm of the human X chromosome (Xp) exhibits many unique and interesting features. Distal Xp contains the pseudoautosomal region, a number of disease loci, and several cell-surface markers. Several genes in this area have also been observed to escape X-chromosomal inactivation. The chara...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Monosomy for the X chromosome in humans creates a genetic Achilles' heel for nature to deal with. We report that the human X chromosome appears to have one-third the density of the coding sequence of the autosomes and, because of partial shielding from the high mutation rate of the male sex, that it should also have a...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/303010
更新日期：2000-08-01 00:00:00
abstract：:Hermansky-Pudlak syndrome (HPS) is genetically heterogeneous, and mutations in seven genes have been reported to cause HPS. Autozygosity mapping studies were undertaken in a large consanguineous family with HPS. Affected individuals displayed features of incomplete oculocutaneous albinism and platelet dysfunction. Ski...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/499338
更新日期：2006-01-01 00:00:00
abstract：:The debrisoquine/sparteine polymorphism is associated with a clinically important genetic deficiency of oxidative drug metabolism. From 5% to 10% of Caucasians designated as poor metabolizers (PMs) of the debrisoquine/sparteine polymorphism have a severely impaired capacity to metabolize more than 25 therapeutically u...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:Estimation of the components of variance for a quantitative trait allows one to evaluate both the degree to which genetics influences the trait and the trait's underlying genetic architecture. For particular traits, the estimates also may have implications for discriminating between potential models of selection and f...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/320112
更新日期：2001-05-01 00:00:00
abstract：:The association between normal alleles at the CTG repeat and two nearby polymorphisms in the myotonin protein kinase gene, the Alu insertion/deletion polymorphism and the myotonic dystrophy kinase (DMK)(G/T) intron 9/HinfI polymorphism, has been analyzed in South African Negroids, a population in which myotonic dystro...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
abstract：:A reproducible and convenient method for assaying glucocerebrosidase activity using the natural substrates has been developed. From the insoluble pellet fraction of cultured skin fibroblast homogenates, released glucose was measured enzymically using hexokinase coupled with the glucose-6-phosphate dehydrogenase (G6PD)...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1980-09-01 00:00:00
abstract：:An elevated level of erythrocyte sodium-lithium (Na-Li) countertransport has been suggested as a predictor of predisposition to essential hypertension. In order to evaluate whether a single genetic or environmental factor with large effects explains the mixture of distributions in Na-Li countertransport in the general...
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：:Recurrent somatic variants in SPOP are cancer specific; endometrial and prostate cancers result from gain-of-function and dominant-negative effects toward BET proteins, respectively. By using clinical exome sequencing, we identified six de novo pathogenic missense variants in SPOP in seven individuals with development...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2020.02.001
更新日期：2020-03-05 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：:Primary hyperoxaluria (PH) is an autosomal-recessive disorder of endogenous oxalate synthesis characterized by accumulation of calcium oxalate primarily in the kidney. Deficiencies of alanine-glyoxylate aminotransferase (AGT) or glyoxylate reductase (GRHPR) are the two known causes of the disease (PH I and II, respect...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.07.023
更新日期：2010-09-10 00:00:00
abstract：:The autosomal dominant cerebellar ataxias (ADCA) type I are a group of neurological disorders that are clinically and genetically heterogeneous. Two genes implicated in the disease, SCA1 (spinal cerebellar ataxia 1) and SCA2, are already localized. We have mapped a third locus to chromosome 14q24.3-qter, by linkage an...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:A family history of coronary artery disease (CAD), especially when the disease occurs at a young age, is a potent risk factor for CAD. DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis. We performed a genomewide sc...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/423900
更新日期：2004-09-01 00:00:00
abstract：:Experiments designed to illuminate the mechanism by which folic acid and thymidine inhibit expression of the Xq28 fragile site in human lymphocytes are described. The fragile site is induced by 5-fluorodeoxyuridine (FUdR), a potent inhibitor of thymidylate synthetase, in the presence of otherwise inhibiting concentrat...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
abstract：:A population-based study of hemophilia B mutations was conducted in the United Kingdom in order to construct a national confidential database of mutations and pedigrees to be used for the provision of carrier and prenatal diagnoses based on mutation detection. This allowed the direct estimate of overall (micro), male ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302651
更新日期：1999-12-01 00:00:00
abstract：:One approach frequently used for identifying genetic factors involved in the process of a complex disease is the comparison of patients and controls for a number of genetic markers near a candidate gene. The analysis of such association studies raises some specific problems because of the fact that genotypic and not g...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mut...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:The elucidation of the largely unknown transcriptome of small RNAs is crucial for the understanding of genome and cellular function. We report here the results of the analysis of small RNAs (< 50 nt) in the ENCODE regions of the human genome. Size-fractionated RNAs from four different cell lines (HepG2, HelaS3, GM0699...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2008.02.016
更新日期：2008-04-01 00:00:00
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, ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1980-07-01 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：:An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift mutations and one de novo m...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.05.007
更新日期：2013-07-11 00:00:00
abstract：:Families in which both parents are heterozygotes for the same autosomal dominant neoplasia syndrome are extremely unusual. Recently, we had the unique opportunity to evaluate three symptomatic siblings from the union between two unrelated individuals affected by multiple endocrine neoplasia type 1 (MEN1). When the thr...
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：:A study was undertaken to characterize the mutation(s) responsible for Tay-Sachs disease (TSD) in a Cajun population in southwest Louisiana and to identify the origins of these mutations. Eleven of 12 infantile TSD alleles examined in six families had the beta-hexosaminidase A (Hex A) alpha-subunit exon 11 insertion m...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:We have previously shown that rheumatoid arthritis (RA) risk alleles overlap between different ethnic groups. Here, we utilize a multiethnic approach to show that we can effectively discover RA risk alleles. Thirteen putatively associated SNPs that had not yet exceeded genome-wide significance (p < 5 × 10(-8)) in our ...
journal_title：American journal of human genetics
pub_type： 杂志文章,meta分析
doi：10.1016/j.ajhg.2012.01.010
更新日期：2012-03-09 00:00:00
abstract：:To quantify the effect of the apolipoprotein (apo) E polymorphism on the magnitude of postprandial lipemia, we have defined its role in determining the response to a single high-fat meal in a large sample of (N = 474) individuals taking part in the biethnic Atherosclerosis Risk in Communities Study. The profile of pos...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
abstract：:The data base of an ongoing population-based registry with multiple sources of ascertainment was used to estimate the present population load from genetic disease in more than 1 million consecutive live births. It was found that, before approximately age 25 years, greater than or equal to 53/1,000 live-born individual...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
abstract：:Autosomal dominant progressive external ophthalmoplegia (adPEO) is a disorder characterized by ptosis, progressive weakness of the external eye muscles, and general muscle weakness. The patients have multiple deletions of mtDNA on Southern blots or in PCR analysis of muscle DNA and a mild deficiency of one or more res...
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 gene for human apolipoprotein C2 (APOC2), situated on the proximal long arm of chromosome 19, is closely linked to the gene for the most common form of adult muscular dystrophy, myotonic dystrophy (DM). Six APOC2 RFLPs (TaqI, BglI, BanI, BamHI, NcoI, and AvaII) have been identified to date. We have conducted a com...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：:The frequencies of different HLA-A and -B alleles in 77 Australian patients with hemochromatosis have been compared with frequencies of HLA alleles not associated with hemochromatosis in 63 of their heterozygous relatives and with published population frequencies. As for all other populations reported, an association ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:Several RFLPs have been detected using a cDNA fragment encoding the amino-terminal half of the A subunit of factor XIII. The RFLPs show little linkage disequilibrium and form many different haplotypes that can be used to identify chromosomes transmitting factor XIII A subunit deficiency. Southern blot analysis of thre...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
