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At least 1,135 records · Page 63Linked to original sources
PubMed2003

Estimation of infection and recovery rates for highly polymorphic parasites when detectability is imperfect, using hidden Markov models.

A Bayesian hierarchical model is proposed for estimating parasitic infection dynamics for highly polymorphic parasites when detectability of the parasite using standard tests is imperfect. The parasite dynamics are modelled as a non-homogeneous hidden two-state Markov process, where the observed process is the detection or failure to detect a parasitic genotype. This is assumed to be conditionally independent given the hidden process, that is, the underlying true presence of the parasite, which evolves according to a first-order Markov chain. The model allows the transition probabilities of the hidden states as well as the detectability parameter of the test to depend on a number of covariates. Full Bayesian inference is implemented using Markov chain Monte Carlo simulation. The model is applied to a panel data set of malaria genotype data from a randomized controlled trial of bed nets in Tanzanian children aged 6-30 months, with the age of the host and bed net use as covariates. This analysis confirmed that the duration of infections with parasites belonging to the MSP-2 FC27 allelic family increased with age.

Algorithms↗
PubMed2002

Characterization of human soluble high and low activity catechol-O-methyltransferase catalyzed catechol estrogen methylation.

The major detoxification pathway of the carcinogenic catechol estrogens is methylation by catechol- -methyltransferase (COMT). It has been hypothesized that the enzyme encoded by the low-activity allele (COMT(L) ) has a lower catalytic activity for catechol estrogen methylation than that encoded by the high activity allele (COMT(H) ). We expressed and purified human soluble (S)-COMT(H) and S-COMT(L) in and characterized the methylation of 2- and 4-hydroxyestradiol (2- and 4-OH-E2). There were no differences between the kinetic parameters for COMT(H) and COMT(L). The kinetic parameters for S-adenosylmethionine (SAM), the methyl donor in these reactions, also did not differ for COMT(H) and COMT(L). S-adenosylhomocysteine, the demethylated SAM metabolite, inhibited methylation of the catechol estrogens in a non-competitive manner similarly for COMT(H) and COMT(L). Each COMT substrate tested inhibited the methylation of other substrates in a mixed competitive and non-competitive fashion similarly for COMT(H) and COMT(L). Furthermore, in cytosolic fractions of COMT(HH)(MCF-10A and ZR-75-1) and COMT(LL)(MCF-7 and T47D) human breast epithelial cell lines, no differences were detected between the kinetic parameters of COMT with respect to 2- and 4-OH-E2 methylation; nor were COMT protein levels associated with the COMT genotype. These data suggest that the decreased COMT enzymatic activity that has been detected in human tissue in association with the COMT(L) allele is not reflected by differences in the affinity or capacity of COMT(H) and COMT(L) for catechol estrogen methylation. These results raise the question of what accounts for the difference in COMT activity associated with the COMT(HH) and COMT(LL) genotypes in human tissue.

Base Sequence↗
PubMed2001

Rapid and simple phenotypic assay for drug susceptibility of human immunodeficiency virus type 1 using CCR5-expressing HeLa/CD4(+) cell clone 1-10 (MAGIC-5).

We describe a rapid and simple novel phenotypic assay for drug susceptibility of human immunodeficiency virus type-1 (HIV-1) using a CCR5-expressing HeLa/CD4(+) cell clone 1-10 (MAGIC-5). MAGIC-5 cells produced large amounts of HIV-1 in culture supernatants, which enabled us to perform the phenotypic resistance assay. Determination of HIV-1 susceptibility to various protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors was completed within 15 days in T-cell-tropic (X4) and macrophage-tropic (R5) viruses using fresh plasma samples containing at least 10(4) copies/ml. The nucleotide sequence of the envelope V3 region of HIV-1 in plasma was almost identical to that of the virus isolated by MAGIC-5 cells, suggesting a lack of selection bias in our assay. The assay variability was confined to within five-fold in all drugs examined. Accordingly, we used a 10-fold increase in the 50% inhibitory concentration as the cutoff value for viral resistance in the present assay. HIV-1 resistant to lamivudine, which was not detected by conventional genotypic assays, was isolated. In HIV-1 with PI-associated primary amino acid substitutions, our assay showed that drug resistance profiles correlated well with previously reported genotypic-assay data. Furthermore, our assay provided comprehensive results regarding PI resistance in the presence of multiple mutations. The novel assay successfully quantified the level of resistance of clinical HIV-1 isolates to a battery of anti-HIV drugs, indicating its clinical usefulness, particularly in patients who failed to respond to antiretroviral chemotherapy.

Amino Acid Sequence↗
PubMed2004

The application of an automated allele concordance analysis system (CompareCalls) to ensure the accuracy of single-source STR DNA profiles.

A powerful method for validating a scientific result is to confirm specific results utilizing independent methodologies and processing pathways. Thus, we have designed, developed and validated an automated allele concordance analysis system (CompareCalls, patent pending) that performs comparisons between two independent DNA analysis platforms to ensure the highest accuracy for allele calls. Application of this system in a quality assurance role has shown the potential to eliminate greater than 90% of the STR analysis required of a DNA data analyst. While this system is broadly applicable for use with any two independent STR analysis programs, either prior to or following human data review, we are presenting its application to data generated with the ABI Prism Genotyper software system versus data generated with the SurelockID system. With the automated allele concordance analysis system, the GeneScan DNA fragment data generated from an ABI 377 gel image are analyzed in two independent pathways. In one analysis pathway, the GeneScan data are imported into Genotyper software where STR labels are assigned to the fragment data based upon the criteria of the Kazam 20% macro. The "Kazam" macro provided with the Genotyper program works by labeling all peaks in a category (or locus) and then filtering (or removing) the labels from peaks, such as those in stutter positions, that meet predefined criteria. In the second pathway, the GeneScan data are imported into the SurelockID analysis platform where STR labels and error messages are assigned to the fragment data based upon hard-coded allele calling criteria and quality parameters. The resulting STR allele calls for each analysis platform are then compared, utilizing the automated allele concordance analysis system. Any differences in the STR allele calls between the two systems are flagged in a discordance report for further review by a qualified DNA data analyst. The automated allele concordance analysis system guides the DNA data analyst to the discordant data generated by either analysis platform. Additionally, the analyst is also directed to data that are of less than pristine quality which may have an increased potential for errors in interpretation by either analysis platform or by a human DNA data analyst. Implementation of an automated allele concordance analysis system will yield high-quality data for CODIS and free the human DNA data analyst to perform other critical duties within the laboratory.

Alleles↗
PubMed2005

Inferring candidate genes for attention deficit hyperactivity disorder (ADHD) assessed by the World Health Organization Adult ADHD Self-Report Scale (ASRS).

The present study tests the psychometric properties and validity of the German version of the World Health Organization Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS), which is a short screening instrument for use in the general population. Furthermore, two candidate genes for ADHD, the COMT VAL158MET and the 5-HT2a T102C polymorphisms, were tested for associations with the ASRS subscales inattention and hyperactivity/impulsivity in N = 203 healthy subjects. The ordinal CFA yielded a two-factorial model corroborating the structure of the official English WHO version. Genetic analysis revealed an association between the VAL allele of COMT and the inattention scale (F(1, 201) = 7.20, p = 0.008), the hyperactivity/impulsivity scale (F(1, 201) = 4.30, p = 0.039), and the total ASRS scale (F(2, 201) = 7.64, p = 0.006) with highest scores in carriers of the MET/MET genotype. The C-allele of 5-HT2a was significantly associated with the hyperactivity/impulsivity scale (F(1, 201) = 5.52, p = 0.020) and the total ASRS scale (F(1, 201) = 4.21, p = 0.042) with highest scores in carriers of the TT genotype. The data provide evidence for the structural as well as for the external validity of the ASRS.

Attention Deficit Disorder with Hyperactivity↗
PubMed1999

Ovarian follicular growth and maturity and follicular production of progesterone and oestradiol in response to porcine luteinising hormone and porcine follicle stimulating hormone in albino (S*AS) hens in vivo and in vitro.

The effects of the SAS gene on follicular growth were studied by feeding Sudan IV and Sudan Black B, on follicular maturity by measuring P4 and E2 output of the 5 largest follicles (F1 to F5) in vitro, and on ovarian response (plasma progesterone, P4, and oestradiol, E2) to administration of porcine follicle-stimulating hormone (pFSH) and porcine luteinising hormone (pLH) in old laying hens. Albino hens had fewer dye rings in the yolks of their eggs than non-albinos (8.32 compared to 8.59) and the yolks from albinos weighed less. The numbers of normal and atretic follicles larger than 3 mm in diameter did not differ between the two genotypes. The P4 outputs from the F1 and F2 follicles were significantly greater for albino hens, but P4 production of other follicles was not different for the two genotypes. The P4 output of the F1 follicle in response to pLH was dose-dependent and greater for albino hens than for non-albinos. Porcine LH did not increase the follicular E2 output in either genotype. Administration of pLH, but not pFSH, increased plasma P4 and E2 concentrations, with no difference between genotypes. These data suggest that the F1 follicles for albino hens are precocious, resulting in a reduced growth period and a smaller weight at ovulation.

Aging↗
PubMed2003

Combined marginal folate and riboflavin status affect homocysteine methylation in cultured immortalized lymphocytes from persons homozygous for the MTHFR C677T mutation.

Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor for the synthesis of methionine from homocysteine. A common C677T mutation in the MTHFR gene renders the enzyme approximately 50% less active than the wild-type enzyme as shown in in vitro studies using cell extracts. We developed an immortalized cell culture model to determine whether the lower in vitro activity imparted by the homozygous (T/T) genotype is demonstrated in situ when exposed to adequate and marginal physiologic concentrations of folate and riboflavin. T/T MTHFR activity was compared with that of C/C genotype cell extracts by an in vitro assay and in intact cells by measuring the distribution of folate forms, the accumulation of homocysteine in the medium and the synthesis of methionine from formate and homocysteine. Under adequate nutrient conditions, the in vitro activity of the T/T MTHFR enzyme was approximately half that of the C/C genotype. Similarly, the proportion of 5-methyltetrahydrofolate in cells with the T/T genotype was approximately half that of the cells with wild-type MTHFR. In contrast, homocysteine accumulation in the culture medium was low and not different between genotypes, nor was there a difference in methionine synthetic capacity. Significant differences were observed between genotypes only when the supply of both folate and riboflavin was limited in the medium, which resulted in increased homocysteine accumulation and decreased methionine production in the T/T genotype. These data are consistent with the current understanding of the molecular interaction of the MTHFR mutant with folate substrates and the FAD prosthetic group.

Cell Transformation, Viral↗
PubMed2003

Association analysis of gamma 2 subunit of gamma- aminobutyric acid type A receptor polymorphisms with febrile seizures.

An alternation of gamma-aminobutyric acid (GABA)-ergic neurotransmission has been implicated as an etiologic factor in epileptogenesis. Missense mutations in the GABRG2 gene, which encodes the gamma2 subunit of central nervous GABAA receptors, have recently been described in one family with childhood absence epilepsy and febrile seizures (FSs). FSs represent the majority of childhood seizures and have a genetic predisposition. It is not known, however, whether polymorphisms in those genes involved in familial epilepsies also contribute to the pathogenesis of FSs. By performing an association study, we used single-nucleotide polymorphisms to investigate the distribution of genotypes of GABRG2 in patients with FSs. A total of 104 children with FSs and 83 normal control subjects were included in the study. PCR was used to identify the C/T and A/G polymorphisms of the GABRG2 gene on chromosome 5q33. Genotypes and allelic frequencies for the GABRG2 gene polymorphisms in both groups were compared. The GABRG2 (nucleotide position 3145 in intron G-->A) gene in both groups was not significantly different. In contrast, the number of individuals with the GABRG2 (SNP211037)-C/C genotype in patients with FSs was significantly greater compared with that in healthy control subjects (p = 0.017), and the GABRG2 (SNP211037)-C allele frequency in patients with FSs was significantly higher than that in healthy control subjects (p = 0.009). The odds ratio for developing FSs in individuals with the GABRG2 (SNP211037)-C/C genotype was 2.56 compared with individuals with the GABRG2 (SNP211037)-T/T genotype. These data suggest that the GABRG2 gene might be one of the susceptibility factors for FSs.

Child↗
PubMed2000

Methylenetetrahydrofolate reductase mutation (677C-->T) negatively influences plasma homocysteine response to marginal folate intake in elderly women.

Individuals who are homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C --> T mutation have depressed serum folate (SF) and elevated plasma total homocysteine (tHcy) concentrations, which may affect folate requirements and increase the risk for coronary artery disease. A controlled metabolic study (14 weeks) using a depletion/repletion protocol was performed in women (aged 60 to 85 years, N = 33) to provide age-specific data on the effects of the MTHFR mutation on SF and tHcy status. Subjects consumed a moderately folate-deplete diet (118 microg/d) for 7 weeks, followed by 7 weeks of folate repletion with 200 or 415 microg/d provided as two different treatments. Following folate depletion, the mean SF concentration was lower for homozygous (P = .017) versus heterozygous subjects. Homozygotes for the 677C --> T mutation showed a higher (P = .015) percent increase in plasma tHcy (44%) than heterozygous (20%) or normal (15%) subjects. At week 7, the mean plasma tHcy concentration was higher in homozygous subjects (12.5 +/- 5.3 micromol/L, mean +/- SD) versus the heterozygous (10.8 +/- 3.8 micromol/L, P = .008) or normal (11.3 +/- 2.7 micromol/L, P = .001) genotype groups. Following folate repletion, plasma tHcy concentrations were not different between genotype groups, despite a higher (P < .016) SF concentration in subjects with the homozygous genotype. These data suggest that older women who are homozygous for the MTHFR 677C --> T mutation may be at risk for greater elevations in plasma tHcy in response to moderately low folate intake as compared with individuals with the normal or heterozygous genotypes.

Aged↗
PubMed2001

Smoking, folate and methylenetetrahydrofolate reductase status as interactive determinants of adenomatous and hyperplastic polyps of colorectum.

Most studies demonstrate increased risk of colorectal cancer (CRC) and adenomas in folate-deficient subjects or that high folate intake may afford some protection. Smoking increases such risk in some but not all studies. We investigated whether smoking, folate status and methylenetetrahydrofolate reductase (MTHFR) genotype predict the risk of adenomatous and hyperplastic polyps of colorectum. By colonoscopy, the type, number, size and extent of dysplasia of colorectal polyps were assessed in 443 subjects aged 63-72 years. We also determined RBC folate and the C667T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Smoking, folate status and the C677T MTHFR polymorphism were strong, interactive determinants of high-risk adenomas (HRAs, defined as adenomas > or =10 mm in diameter, adenomas with villous components or with severe dysplasia). The risk was particularly high in smokers with low folate and the CT/TT genotype (risk category T) and in smokers with high folate and the CC genotype (risk category C). With non-smokers with low folate and the CC genotype as reference, the odds ratios (OR, 95% CI) were 8.7 (2.5-29.7) in category T and 9.9 (2.6-38.4) in category C. Notably, this risk pattern was also observed for hyperplastic polyps. In conclusion, in smokers, high folate status may confer increased or decreased risk for HRAs, depending on the MTHFR genotype. These data demonstrate the strong gene-nutrition interaction involving the C677T MTHFR polymorphism.

Adenomatous Polyps↗
PubMed1998

DD genotype of the angiotensin I-converting enzyme gene is a risk factor for early onset of essential hypertension in Japanese patients.

Although angiotensin-converting enzyme (ACE) plays an important role in blood pressure regulation, no relationship between the insertion/deletion (I/D) polymorphism of the ACE gene and essential hypertension has been observed. However, as the pathogenesis and genetic background of essential hypertension are heterogeneous, we investigated whether the ACE gene is a marker of subgroups of patients with essential hypertension. A group of 178 patients with essential hypertension (90 men/88 women; 53 +/- 13 years of age, mean age +/- SD ) and 101 normotensive control subjects (54 men/47 women; 51 +/- 14 years of age, mean age +/- SD ) were included in the study. The allele frequencies of the two groups were similar. There were no differences in age, blood pressure, retinopathy grade, presence of proteinuria, or resting plasma renin activity (PRA) among the hypertensive patients with the II, ID, and DD genotypes. However, the age of onset of hypertension of patients with the DD genotype was lower (p < 20.05) and their left ventricular mass index was higher (p < 2 0.05) than those in patients with the non-DD genotype. These data suggest that the I/D polymorphism of the ACE gene is associated with an early onset of hypertension and left ventricular hypertrophy in Japanese patients with essential hypertension.

Adult↗
PubMed2005

Association of CYP2A6*1B genetic variant with the amount of smoking in French adults from the Stanislas cohort.

This study was designed in order to investigate the influence of the genetic polymorphism of CYP2A6 on the amount of smoking. In all, 463 French adults included in the Stanislas cohort were studied and underwent two examinations at 5 years distance (t0 and t(+5) years). Information on their smoking habits was collected. They were genotyped by RFLP for the CYP2A6*1A, CYP2A6*1B and CYP2A6*4 alleles. CYP2A6*1B and CYP2A6*4 allele frequencies were 32 and 4%, respectively. The subjects carrying the CYP2A6*1B allele oxidize nicotine to cotinine faster than subjects with the CYP2A6*1A allele. The number of cigarettes smoked per day was significantly higher in the CYP2A6*1B/*1B group as compared to the CYP2A6*1A/*1A group (P = 0.01 at t0; P = 0.001 t(+5) years), with a larger increase in their daily cigarettes consumption over the 5-year period (P = 0.006). No significant difference in the smoking status was observed according to the CYP2A6 genotype. These data suggest that the CYP2A6*1B is associated with the number of cigarettes smoked per day.

Adult↗
PubMed2005

Genotype-phenotype correlation between the polymorphic UGT2B17 gene deletion and NNAL glucuronidation activities in human liver microsomes.

The nicotine-derived tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is one of the most potent and abundant procarcinogens found in tobacco and tobacco smoke, and glucuronidation of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), is an important mechanism for NNK detoxification. In cigarette smokers and tobacco chewers, there is a wide variation in the urinary levels of the ratio of NNAL to NNAL glucuronide (NNAL-Gluc). To determine whether genetic variation plays a potential role in this inter-individual variability, NNAL-glucuronidating activities were analysed in a series of human liver microsomal specimens and compared with UGT2B17 deletion genotypes in the same subjects. Assays performed in vitro demonstrated that over-expressed UGT2B17 exhibits high O-glucuronidating activity against NNAL. When stratifying subjects by UGT2B17 genotype, a significant or near-significant decrease in NNAL-O-Gluc formation was observed in liver microsomes from individuals who were either heterozygous [(+/0), P=0.07] or homozygous [(0/0), P=0.016] for the UGT2B17 deletion compared to liver microsomes from individuals with intact UGT2B17 alleles [(+/+)]. There was a significant (P<0.01) association between the level of liver microsomal NNAL-O-glucuronide formation and increasing numbers of the UGT2B17 null alleles in the liver microsomal specimens examined in this study, and a significant decrease in NNAL-O-Gluc formation was observed when comparing liver microsomes from individuals who had at least one UGT2B17 allele deleted [(+/0)+(0/0)] versus microsomes from UGT2B17 (+/+) subjects (P=0.004). When stratifying by the median value of NNAL-O-Gluc formation activity, a significantly (P=0.015) higher number of subjects with liver microsomes having low NNAL-O-Gluc formation activity contained the UGT2B17 null genotype compared to subjects with liver microsomes exhibiting high NNAL-O-Gluc formation activity. When stratifying by UGT2B7/UGT2B17 haplotypes, the association between the level of liver microsomal NNAL-O-glucuronide formation and increasing numbers of the UGT2B17 null allele was at the level of statistical significance for subjects with the UGT2B7 (*1/*2) (P=0.05) or UGT2B7 (*2/*2) (P<0.02) genotypes. These data suggest that the UGT2B17 deletion polymorphism is associated with a reduced rate of NNAL detoxification in vivo and may increase individual susceptibility to tobacco-related cancers.

Base Sequence↗
PubMed2003

Haplotype analysis of the human renin gene and essential hypertension.

The human renin gene is an attractive candidate for involvement in the underlying cause of essential hypertension (EH). Despite extensive examination, the relation between the renin gene and hypertension remains unclear. The aims of the present study were to discover new genetic markers of EH and to investigate the relations between polymorphisms of the renin gene and EH in the Japanese. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we isolated 3 novel variants of the renin gene; a single nucleotide polymorphism (SNP) in intron 4 (T+17int4G), a variable number of tandem repeats (VNTR) polymorphism in intron 7, and a missense mutation in exon 9 (G1051A). We performed an association study with these polymorphisms in 212 patients with EH and 209 age-matched normotensive (NT) subjects. The frequency of genotypes VNTR and T+17int4G did not differ significantly between the 2 groups, whereas the overall distribution of G1051A was significantly different between EH and NT. Haplotype analysis revealed that the overall distribution of haplotypes differed significantly between the EH and NT groups. PRA levels in patients with EH with the G/G genotype were significantly higher than in subjects with EH with G/A and A/A genotypes. These data suggest that the missense mutation in exon 9 may affect the enzymatic function of renin and consequently may be involved in the etiology of hypertension.

Adult↗
PubMed1996

[Analysis of HCV infection in patients with hemophilia].

Second generation antibodies of HCV, HCV-RNA, genotype and data of liver function were investigated with the purpose of better understanding the condition of the 32 hemophiliac patients currently in our hospital. The results being: 1) The positivity ratio of second generation antibodies was 96.9% and a negative example occurred in only one infant born in 1990. 2) In the positive example of second generation antibodies, HCV-RNA positivity was 77.4%, which is extremely high result. 3) There are several kinds of genotypes, such as type I, type II, type II + III and type III. Type I is most commonly found in the younger generation. The possibly for this presence was suggested to be from imported blood products. 4) There were few findings of liver disorder in cases of HCV-RNA negative patients. Meanwhile, the presence of liver disorder was found in about 70% HCV-RNA patients. There is evidence of correlation between the level disorder and age of the patient. In general, initial infection for hemophiliac patients takes place early in life. Compared to non-hemophilia hepatitis C patients, the liver disorder occurs at all ages but is becoming more prevalent younger patients. Although not common, there were occasionally a few cases of liver disorder turning into cirrhosis of the liver in patients in their 30's.

Adolescent↗
PubMed1996

A rapid method to study heat shock protein 70-2 gene polymorphism in insulin-dependent diabetes mellitus.

To examine the role of DNA loci within the human leukocyte antigen (HLA) region and insulin-dependent diabetes mellitus (IDDM), we studied fine mapping of HSP70-2 gene. Polymerase chain reaction (PCR)-based genotyping was then developed and applied to type HSP70-2 in 59 patients with IDDM and 83 unrelated controls recruited from the inhabitants of northern Taiwan. Southern blot analysis revealed a diallelic PstI polymorphism of the HSP 70-2 gene, i.e., 9.6- and 8.5-kb alleles. The polymorphic site was mapped in the intragenic PstI sequences (nucleotides 1051-1056) of the HSP70-2 gene. PCR-based restriction fragment length polymorphism studies revealed that the frequency of the 8.5-kb allele was increased in IDDM (56.8%, vs. 40.4% in controls; p < 0.009), with a relative risk of 1.93 (95% confidence interval = 1.20-3.11). The genotypic frequencies of 9.6/9.6, 9.6/8.5, and 8.5/8.5 were 17.0, 52.5, and 30.5% for IDDM were different from those of controls (36.1, 47.0, and 16.9%, respectively; the homozygous 9.6/ 9.6 genotype was significantly decreased in the IDDM group, p < 0.02). In conclusion, we provide a simple, rapid, and nonradioactive method for HSP70-2 genotyping. Our data confirmed that the 8.5-kb allele of HSP70-2 was associated with IDDM susceptibility in the Taiwanese population.

Adult↗
PubMed1998

Incorporating genotypes of relatives into a test of linkage disequilibrium.

Genetic data from autosomal loci in diploids generally consist of genotype data for which no phase information is available, making it difficult to implement a test of linkage disequilibrium. In this paper, we describe a test of linkage disequilibrium based on an empirical null distribution of the likelihood of a sample. Information on the genotypes of related individuals is explicitly used to help reconstruct the gametic phase of the independent individuals. Simulation studies show that the present approach improves on estimates of linkage disequilibrium gathered from samples of completely independent individuals but only if some offspring are sampled together with their parents. The failure to incorporate some parents sharply decreases the sensitivity and accuracy of the test. Simulations also show that for multiallelic data (more than two alleles) our testing procedure is not as powerful as an exact test based on known haplotype frequencies, owing to the interaction between departure from Hardy-Weinberg equilibrium and linkage disequilibrium.

Genetic Diseases, Inborn↗
PubMed2004

Genotypic analysis of sequential genital herpes simplex virus type 1 (HSV-1) isolates of patients with recurrent HSV-1 associated genital herpes.

Clinical recurrences of Herpes simplex virus type 1 (HSV-1)-associated genital herpes are thought to be caused by reactivation of latent endogenous HSV-1. However, the possibility of reinfection with exogenous HSV-1 cannot be excluded. This study aimed to determine the incidence of genital HSV-1 superinfection in patients by investigating the genotype of sequential HSV-1 isolates obtained from the same anatomical site of patients with clinical recurrences of genital HSV-1 recurrent genital herpes. Sequential genital HSV-1 isolates were genotyped by PCR amplification of the hypervariable regions located within the HSV-1 genes US1 and US12. Whereas the sequential HSV-1 isolates in 11 of the 13 patients studied had the same genotypes, the sequential isolates of 2 patients showed a different genotype. The data suggest that HSV-1-induced recurrent genital herpes can be associated with genital reinfection with an exogenous HSV-1 strain.

Adult↗