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11.
Detection of chromosomes and estimation of aneuploidy in human spermatozoa using fluorescence in-situ hybridization 总被引:11,自引:0,他引:11
The development and application of fluorescence in-situ hybridization
(FISH) has opened the way for comprehensive studies on numerical chromosome
abnormalities in human spermatozoa. FISH can be rapidly applied to large
numbers of spermatozoa and thus overcomes the major limitation of
karyotyping spermatozoa after penetration of zona-free hamster oocytes. The
simultaneous hybridization of two or more chromosome-specific probes to
spermatozoa and subsequent detection of the bound probes using different
fluorescent detection systems enables two or more chromosomes to be
localized simultaneously in the same spermatozoon and provides a technique
for undertaking reasonable estimates of aneuploidy. The most commonly used
probes are those which bind to the centromeric region of specific
chromosomes. Most studies to date have concentrated on estimating
aneuploidy in spermatozoa from normospermic men, although reports are
beginning to appear on aneuploidy in spermatozoa from subfertile and
infertile men. Multi- probe FISH studies have generally reported disomy
(hyperhaploidy) estimates of 0.05-0.2% per chromosome. There is preliminary
evidence that some chromosomes such as X, Y and 21 are predisposed towards
higher rates of non-disjunction during spermatogenesis. There are also
suggestions of inter-donor variability in aneuploidy frequencies for
specific chromosomes, although this requires confirmation in larger
studies. While FISH is clearly a powerful technique that has many
applications in reproductive medicine, it must also be realized that it
does have limitations and the technology itself is still evolving and has
yet to be fully validated on spermatozoa.
相似文献
12.
Smoking is a major risk factor for coronary heart disease (CHD), but this risk may be modified by an individual's genotype. A common functional 5A/6A polymorphism in the promoter of the stromelysin-1 (matrix metalloproteinase 3, MMP3) gene has been identified. The 6A allele has been consistently associated with faster progression of angiographically determined CHD, while the 5A allele has recently been associated with risk of acute myocardial infarction (MI) in patients with unstable angina. To date there has been no prospective study of the relationship of this genotype to CHD risk in smokers and non-smokers. DNA was available from 2,743 middle-aged men, free of CHD at baseline, recruited through nine general practices in the UK for prospective surveillance. To date there have been almost 24,000 person-years of follow-up with 125 CHD events (fatal and non-fatal MI, sudden coronary death, need for coronary artery surgery or new major ECG Q-wave abnormality). Men with events were each matched for age, practice and cholesterol level with three healthy men. Smoking habit was determined by questionnaire. 5A/6A genotype was determined using a heteroduplex generator method. Associations between genotype and disease outcome, according to smoking status, were assessed using conditional logistic regression. Overall, current smoking was associated with a relative risk (RR) of 1.99 (95% CI 1.30-3.06) as compared with never-smokers and ex-smokers combined (p&0.002). In non-smoking men, and after adjustment for conventional risk factors, compared with the 5A5A group, the RR was 1.37 (0.64-2.94) in those with the genotype 5A6A and 3.02 (1.38-6.61) in those with the genotype 6A6A. Smoking increased risk 1.4 fold in the 5A6A group to 1.91 (1.84-4.36), by 1.3 fold in the 6A6A group to 4.01 (1.57-10.24), but by 3.81 fold (1.54-9.40) in the 5A5A group (smoking-genotype interaction p = 0.01). The data indicate a key role for stromelysin in the atherosclerotic process. Men with the stromelysin genotype 5A5A represent 29% of the general population, and their high risk, if smokers, provides a further strong argument for smoking avoidance. 相似文献
13.
Heritability of C-Reactive Protein and Association with Apolipoprotein E Genotypes in Japanese Americans 总被引:1,自引:0,他引:1
M. A. Austin C. Zhang S. E. Humphries W. L. Chandler P. J. Talmud K. L. Edwards D. L. Leonetti M. J. Mcneely W. Y. Fujimoto 《Annals of human genetics》2004,68(3):179-188
Numerous studies have demonstrated that increased C‐reactive protein (CRP) levels predict coronary heart disease, stroke, peripheral vascular disease, and diabetes, and are associated with features of the metabolic syndrome. Only three previous studies have investigated the heritability of CRP levels, primarily in samples of Caucasian families.The purpose of the present study was to estimate the magnitude of genetic influences on CRP levels, and to examine potential associations between variation in the APOE gene and CRP levels, using a sample of 562 individual Japanese Americans from 68 extended kindreds. In general, correlation coefficients between first‐degree relatives for CRP were approximately 0.2, and spouse correlations did not differ from zero, consistent with genetic influences. Heritability estimates were approximately 0.3 (p < 0.01), even with adjustment for factors known to influence CRP levels. A significant relationship was seen between unadjusted CRP levels and APOE genotypes (p = 0.02), with the highest mean CRP level among ?2 carriers (1.20 mg/L), and nearly the same mean levels among ?3/?3 subjects and ?4 carriers (0.72 and 0.74 mg/L, respectively). However, this relationship was diminished with adjustment for covariates (p = 0.07). These results demonstrate the presence of both genetic and environmental effects on CRP levels among Asian Americans, and additional studies are needed to determine if the APOE gene contributes to these genetic influences. 相似文献
14.
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16.
Transplantation of immunodeficient mice with human hematopoietic cells has greatly facilitated studies of the earliest stages of human hematopoiesis. These include demonstration of the ability of injected 'human-specific' hematopoietic growth factors to enhance the production of human cells at multiple levels of differentiation. In contrast, the effects of continuous exposure to such molecules have not been well investigated. Here, we show that nonobese diabetic severe combined immunodeficiency mice genetically engineered to produce ng/ml serum levels of human interleukin-3 (IL-3), granulocyte/macrophage-stimulating factor (GM-CSF) and Steel factor (SF) display a complex phenotype when transplanted with primitive human bone marrow (BM) or fetal liver cells. This phenotype is characterized by an enhancement of terminal human myelopoiesis and a matched suppression of terminal human erythropoiesis, with a slight reduction in human B-lymphopoiesis in the BM of the engrafted mice. Human clonogenic progenitors are more prevalent in the blood of the transplanted growth factor-producing mice and this is accompanied by a very marked reduction of more primitive human cells in the BM. Our findings suggest that long-term exposure of primitive human hematopoietic cells to elevated levels of human IL-3, GM-CSF and SF in vivo may deleteriously affect the stem cell compartment, while expanding terminal myelopoiesis. 相似文献
17.
A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma 总被引:8,自引:2,他引:8
Chen J; Giovannucci E; Hankinson SE; Ma J; Willett WC; Spiegelman D; Kelsey KT; Hunter DJ 《Carcinogenesis》1998,19(12):2129-2132
We examined the relationship between a functional polymorphism (667C--
>T, ala-->val) of the methylenetetrahydrofolate reductase gene
(MTHFR) and the risk of colorectal adenomas in the prospective Nurses'
Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR
val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval
(CI) 0.84-2.17] was not significantly associated with risk of adenomas.
This lack of association was observed for both small (RR = 1.36, 95% CI
0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore,
there was no significant interaction between this polymorphism and
consumption of either folate, methionine or alcohol. We also examined the
relationship of a newly identified polymorphism (asp919gly) of the
methionine synthase gene (MS) with the risk of colorectal adenomas in the
same population. The MS gly/gly polymorphism was also not significantly
associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70).
These results, which need to be confirmed in other studies, suggest that
the MTHFR val/val polymorphism, which has been previously inversely
associated with risk of colorectal cancer, plays a role only in a late
stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may
protect against malignant transformation in the subset of benign adenomas,
which may progress to malignancy.
相似文献
18.
Suneet P Chauhan Nancy N Lynn Maureen Sanderson Joyce Humphries Jill H Cole James A Scardo 《The journal of maternal-fetal & neonatal medicine》2006,19(11):699-705
OBJECTIVE: To develop a scoring system for the detection of a macrosomic fetus (birth weight (BW) >or= 4000 g) and predict shoulder dystocia among large for gestational age fetuses. STUDY DESIGN: We retrospectively identified all singletons with accurate gestational age (GA) that were large for GA (abdominal circumference (AC) or estimated fetal weight (EFW) >or= 90% for GA) at >or=37 weeks with delivery within three weeks. The scoring system was: 2 points for biparietal diameter, head circumference, AC, or femur length >or=90% for GA, or if the amniotic fluid index (AFI) was >or=24 cm; for biometric parameters <90% or with AFI <24 cm, 0 points. The predictive values for detection of shoulder dystocia were calculated. RESULTS: Of the 225 cohorts that met the inclusion criteria the rate of macrosomia was 39% and among vaginal deliveries (n = 120) shoulder dystocia occurred in 12% (15/120; 95% confidence interval (CI) 7-20%). The sensitivity of EFW >or=4500 g to identify a newborn with shoulder dystocia was 0% (95% CI 0-21%), positive predictive values 0% (95% CI 0-46%), and likelihood ratio of 0. For a macrosomia score >6, the corresponding values were 20% (4-48%), 25% (5-57%) and 2.3. CONCLUSION: Though the scoring system can identify macrosomia, it offers no advantage over EFW. The scoring system and EFW are poor predictors of shoulder dystocia. 相似文献
19.
M D Milsom R Duxbury D Gagen R K Humphries M Schmidt C von-Kalle L J Fairbairn 《Leukemia》2005,19(1):148-153
20.