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At least 1,333 records · Page 74Linked to original sources
PubMed1998

Stromelysin-1 (MMP-3)-independent gelatinase expression and activation in mice.

A potential physiological role of stromelysin-1 (MMP-3) in the expression or activation of gelatinase A (MMP-2) or gelatinase B (MMP-9) in the wall of injured arteries was studied with the use of homozygous MMP-3-deficient (MMP-3-/-) mice. One week after perivascular electric injury of the carotid or femoral artery in wild-type (MMP-3+/+) or MMP-3-/- mice, 70 kD and 65 kD proMMP-2 levels were enhanced by twofold to fourfold, with corresponding increases of 20- to 40-fold for active 61 kD and 58 kD MMP-2, and of 10- to 80-fold for 94 kD proMMP-9. Active MMP-2 species represented approximately one third of the total MMP-2 concentration for both MMP-3+/+ and MMP-3-/- mice. Active 83 kD MMP-9 was not detected in noninjured carotid or femoral arteries, whereas one week after injury its contribution to the total MMP-9 level was 11% to 18% for MMP-3+/+ and MMP-3-/- mice. Immunostaining of arterial sections confirmed enhanced expression of both MMP-2 and MMP-9 after vascular injury. Double immunostaining showed colocalization of MMP-9 with macrophages in the adventitia, whereas MMP-2 was also detected mainly in the adventitia but failed to colocalize with smooth muscle cells. Cell culture experiments confirmed comparable ratios of active versus latent MMP-2 in skin fibroblasts and smooth muscle cells derived from MMP-3+/+ and MMP-3-/- mice. Addition of plasmin(ogen) did not significantly affect activation of proMMP-2. In MMP-3+/+ and MMP-3-/- macrophages, comparable levels of 94 kD proMMP-9 were detected, and plasmin(ogen)-mediated conversion to 83 kD MMP-9 was obtained in both genotypes. These data thus indicate that proMMP-2 activation may occur via a plasmin- and MMP-3-independent mechanism, whereas plasmin can directly activate proMMP-9 via a MMP-3-independent mechanism.

Animals↗
PubMed1999

Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data.

Cytochrome P4502D6 (CYP2D6) is a highly polymorphic gene locus with > 50 variant alleles which lead to a wide range in enzymatic activity. So called poor metabolizers are carriers of any two non-functional alleles of the CYP2D6 gene. CYP2D6 genotyping is cumbersome and the question of how much genotyping is necessary for an accurate phenotype prediction is still debated. The goal of this study was to determine the optimum amount of genotyping required to accurately predict the phenotype at a reasonable cost in a white North American population. To address this issue, we designed a polymerase chain reaction (PCR)/restriction fragment length polymorphism-based genotyping strategy to detect 'key' mutations linked to extensive metabolizer or poor metabolizer associated alleles in combination with extra-long PCR (XL-PCR). All mutations with the exception of gene deletions and duplications are detectable by simple restriction digestion analysis and agarose gel electrophoresis. In addition, we utilized a genotyping algorithm based on our own and published allele frequency data and phenotype analysis to calculate the probability of a correct genotype (and thus, phenotype) assignment. As little as one XL-PCR reaction followed by a maximum of six reamplification reactions allows an accurate prediction of an individual's genotype to 99.15%. As few as four reamplification reactions identify 97.9% of poor metabolizer individuals. We evaluated our model in 208 white North Americans by testing for the presence of 'key' mutations linked to CYP2D6*2, *3, *4, *6, *7, *8, *9, *10, *11, *12, *15, *17 and *18 alleles and the *5, *13 and *16 gene deletions. For all individuals, the correct phenotype has been predicted. Discordant phenotype assignment occurred in only two individuals which subsequently was attributed to CYP2D6 inhibition by concomitant drug therapy.

Algorithms↗
PubMed2006

Evaluation of the ovine callipyge locus: IV. Genotypic effects on reproductive traits.

A resource population of ewes derived from Dorset and Romanov grandparents was generated over 5 yr to provide genotypic and phenotypic data to estimate effects of each callipyge genotype on component traits of reproduction. Effects on ovulation rate were estimated from data recorded by examination of ovaries from serially slaughtered ewe lambs (n = 174) born in 1994 and 1995. Productivity and longevity through 5 yr of age were recorded on a total of 265 F2 ewes produced in 1996 through 1998. Number of lambs born, birth weights, and weaning weights of lambs were calculated for each ewe. Weaning weight was recorded for each lamb and adjusted for age to 56 and 32 d for dam- and nursery-reared lambs, respectively. Longevity was determined as a binary trait based on the presence or absence of the ewe in the breeding flock at 5 yr of age. Ewes generated 937 records for breeding weight and 925 records for conception rate, which was determined on ewes exposed and still present at the start of each lambing season. Seven hundred seventeen records were analyzed for traits based on the number of ewes lambing. Genotypes for the causative callipyge mutation were determined using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay. Each ewe was classified into 1 of 4 genotypes; NMatNPat, NMatCPat, CMatNPat, or CMatCPat, where N represents wild type and C represents the mutant allele. The mean ovulation rate of the ewe lambs genotyped NMatNPat was greater (P < 0.02) than that exhibited by NMatCPat; however, the estimated difference of 0.25 ovum in the ewe lambs did not affect the number born. The live weight of NMatCPat ewes at breeding was 2.5 kg less than that of other genotypes (P < 0.01). The callipyge genotype class did not significantly affect conception rates, fecundity, maternal ability, or ewe longevity. Maintaining a ewe flock to produce homozygous mutant rams for use in terminal sire mating systems presents no unusual problems from a reproduction standpoint.

Animals↗
PubMed2005

Tumour necrosis factor-alpha gene haplotype is associated with pre-eclampsia.

We determined whether polymorphisms in the promoter region of the tumour necrosis factor alpha (TNF-alpha) gene contributes to differences in susceptibility to develop pre-eclampsia. The study involved 133 pre-eclamptic and 115 healthy pregnant women who were genotyped for the G-308A polymorphism of the TNF-alpha gene. The frequency of the G-308A allele was more common in the pre-eclampsia group than among the controls (P=0.046), giving an odds ratio of 0.57 (95% CI: 0.32-0.99), but there were no differences in the genotype distribution. The data from the G-308A polymorphism was combined with the previously published genotype and allele data from the C-850T polymorphism of the TNF-alpha gene, and used to assess a haplotype estimation analysis. Estimated overall pair of loci haplotype frequencies differed significantly between the groups (P=0.023+/-0.004). In the single haplotype association analysis, the haplotype C-A versus others was over-represented in the pre-eclampsia group (P=0.041+/-0.003), whereas the haplotype T-G versus others was less common in the pre-eclampsia group (P=0.035+/-0.003), compared with the controls. In conclusion, the polymorphisms of the TNF-alpha gene showed a significant haplotype association with susceptibility to pre-eclampsia in the Finnish population.

Adult↗
PubMed2006

Histopathology of chronic hepatitis C in relation to virus genotype.

BACKGROUND/AIM: The natural history of hepatitis C virus (HCV) infection is variable and the factors determining the course of the illness are unclear. There are geographical variations in the distribution of different HCV genotypes, and some of them are related to the specific infection routes. Regarding our country, the dominant genotype is genotype 1b. It is unclear and still remains a question whether the distinct histopathological manifestations are related to the particular genotypes of HCV. Thus, the aim of this study was to determine whether the distinct histopathological manifestations of HCV infection might be in relation to the individual virus genotype. METHODS: In this study we examined 126 patients with chronic HCV infection regarding the histopathological features, demographic data, and virus genotype. The observed groups of patients were predominantly infected with HCV genotypes 1b and 3a. RESULTS: In this study we found that the patients infected with HCV genotype 1b had more frequently moderate or severe necroinflammatory activity of the disease, significantly higher grading score as compared with other genotypes (p < 0.0001). A higher degree of fibrosis was, also, more common in the patients infected with genotype 1b of HCV as compared with other genotypes (p < 0.05). There were no significant correlations between the necroinflammatory activity of the disease and the stage of fibrosis in 1b, 4 and mixed genotypes. CONCLUSION: The present data support the hypothesis that distinct genotypes of HCV are associated with the particular histopathological manifestation of the disease.

Adolescent↗
PubMed2005

Characterizing allelic associations from unphased diploid data by graphical modeling.

A method for estimating a graphical model to describe allelic associations between genetic loci is extended to use diploid genotypes rather than haploid data. It also provides haplotype frequency estimates, estimates of phase for sampled individuals, allows for missing or partial information, genotyping errors, and arbitrary penetrance functions. A data set of 688 unrelated individuals genotyped on 25 genetic loci is used to illustrate haplotype frequency estimation. The frequencies obtained are shown to be similar to those obtained by the PHASE program. We also illustrate how putative loci for traits can be included in the analysis in order to detect allele-phenotype associations. Haplotype reconstruction is illustrated on a standard set of 40 male X-chromosome haplotypes, randomly paired to simulate diploid genotype data. The novel method is shown to be comparable to most existing ones, though the PHASE method does consistently better on this problem. The graphical model approach is shown to have some advantages in terms of tractability and can be used to select informative subsets of loci and to map loci influencing phenotypes.

Alleles↗
PubMed2001

Efficient computation of genotype probabilities for loci with many alleles: I. Allelic peeling.

Genetic marker data are likely to be obtained from a relatively small proportion of the individuals in many livestock populations. Information from genetic markers can be extrapolated to related individuals without marker data by computing genotype probabilities using an algorithm referred to as peeling. However, genetic markers may have many alleles and the number of computations in traditional peeling algorithms is proportional to the number of alleles raised to the sixth or eighth power, depending on pedigree structure. An alternative algorithm for computing genotype probabilities of marker loci with many alleles in large, nonlooped pedigrees with incomplete marker data is presented. The algorithm is based on recursive computations depending on alleles instead of genotypes, as in traditional peeling algorithms. The number of computations in the allelic peeling algorithm presented here is proportional to the square of the number of alleles, which makes this algorithm more computationally efficient than traditional peeling for loci with many alleles. Memory requirements are roughly proportional to the number of individuals in the pedigree and the number of alleles. The recursive allelic peeling algorithm cannot be applied to pedigrees that include full sibs or loops. However, it is a preliminary step toward a more complex and encompassing iterative approach to be described in a companion paper.

Alleles↗
PubMed2005

SOP3v2: web-based selection of oligonucleotide primer trios for genotyping of human and mouse polymorphisms.

SOP3v2 is a database-driven graphical web-based application for facilitating genotyping assay design. SOP3v2 accepts data input in numerous forms, including gene names, reference sequence numbers and physical location. For each entry, the application presents a set of recommended forward and reverse PCR primers, along with a sequencing primer, which is optimized for sequence-based genotyping assays. SOP3v2-generated oligonucleotide primer trios enable analysis of single nucleotide polymorphisms (SNPs) as well as insertion/deletion polymorphisms found in genomic DNA. The application's database was generated by warehousing information from the National Center for Biotechnology Information (NCBI) dbSNP database, genomic DNA sequences from human and mouse, and LocusLink gene attribute information. Query results can be sorted by their biological relevance, such as nonsynonymous coding changes or physical location. Human polymorphism queries may specify ethnicity, haplotype and validation status. Primers are developed using SOP3v2's core algorithm for evaluating primer candidates through stability tests and are suitable for use with sequence-based genotyping methods requiring locus-specific amplification. The method has undergone laboratory validation. Of the SOP3v2-designed primer trios that were tested, a majority (>80%) have successfully produced genotyping data. The application may be accessed via the web at http://imgen.ccbb.pitt.edu/sop3v2.

Animals↗
PubMed1997

Genotype relative-risks and association tests for nuclear families with missing parental data.

The development of a new method for testing the association of genetic markers with disease is presented. This approach is applicable when sampling nuclear families with one or more affected siblings and when neither, one, or both parents are missing marker genotype data. All siblings, affected and not affected, are used to probabilistically infer the missing parental marker data. A likelihood ratio statistic, which treats marker allele frequencies as nuisance parameters, is presented to test whether all marker relative risks are equal to one (i.e., no marker association). This approach offers a solution to test for marker associations when parents are difficult to obtain.

Algorithms↗
PubMed2004

Hepatitis E in the south west of France in individuals who have never visited an endemic area.

A total of 431 consecutive patients from the Midi Pyrenees area with acute hepatitis with unknown etiology in 2001-2002 were tested for the presence of immunoglobulin G-class (IgG) anti-hepatitis E virus (HEV) antibodies. Forty-six (10.7%) had anti-HEV IgG, and the results were questionable for a further 17 (3.9%). Real time PCR based on TaqMan detection was used to identify HEV genome fragments in the serum of patients with positive or questionable anti-HEV serology. HEV RNA was found in 25.4% of cases. All amplification products were sequenced and analyzed. Phylogenetic analysis revealed that all the strains were genotype 3. In conclusion, virological and epidemiological data indicate that genotype 3 viruses are circulating in the south west part of France (Midi-Pyrenees) in patients with acute hepatitis and who have not visited recently areas in which HEV is endemic.

Acute Disease↗
PubMed1995

Absence of linkage between familial neural tube defects and PAX3 gene.

Neural tube defects (NTD) are among the most common and disabling birth defects. The aetiology of NTD is unknown and their genetics are complex. The majority of NTD cases are sporadic, isolated, nonsyndromic, and generally considered to be multifactorial in origin. Recently, PAX3 (formerly HuP2, the human homologue of mouse Pax-3), on chromosome 2q35-37, was suggested as a candidate gene for NTD because mutations of Pax-3 cause the mouse mutant Splotch (Sp), an animal model for human NTD. Mutations in PAX3 were also identified in patients with Waardenburg syndrome type 1 (WS1). At least eight patients with both WS1 and NTD have been described suggesting pleiotropy or a contiguous gene syndrome. Seventeen US families and 14 Dutch families with more than one affected person with NTD were collected and 194 people (50 affected) from both data sets were genotyped using the PAX3 polymorphic marker. The data were analysed using affecteds only linkage analysis. The lod scores were -7.30 (US), -3.74 (Dutch), and -11.04 (combined) at theta = 0.0, under the assumption of the autosomal dominant model. For the recessive model, the lod scores were -3.30 (US), -1.46 (Dutch), and -4.76 (combined) at theta = 0.0. Linkage between PAX3 and familial NTD was excluded to 9.9 cM on either side of the gene for the dominant model and to 3.63 cM on either side of the gene for the recessive model in the families studied. No evidence of heterogeneity was detected using the HOMOG program. Our data indicate that PAX3 is not a major gene for NTD.

Base Sequence↗
PubMed2003

Effects of hyperfibrinogenemia on vasculature of C57BL/6 mice with and without atherogenic diet.

OBJECTIVE: Elevated fibrinogen is correlated with severe atherosclerosis, as defined by the occurrence of ischemic events, but the mechanistic basis for this correlation remains unknown. To study this relationship, we examined spontaneous and diet-induced atherosclerosis in transgenic mice with hyperfibrinogenemia (elevated fibrinogen). METHODS AND RESULTS: Normal and transgenic mice were fed either an atherogenic diet or simple breeder chow. We measured plasma fibrinogen levels and identified an age-dependent and diet-dependent increase in fibrinogen. After 8 to 12 months, aortic sections were prepared and stained, and lipid-containing lesions were counted, measured, and assessed for maturity. Lipid-filled deposits appeared spontaneously in a small number of mice on breeder chow; typical fatty streak-type lesions appeared in almost all of the diet-fed animals. Morphometric analysis showed that neither the number nor the size of lesions was influenced by either fibrinogen level or genotype. CONCLUSIONS: Our data showed that neither fibrinogen concentration nor genotype had a statistically significant effect on the initiation, initial growth, or early progression of atherosclerotic lesions.

Animals↗
PubMed2006

Detecting genotype-environment interaction in monozygotic twin data: comparing the Jinks and Fulker test and a new test based on Marginal Maximum Likelihood estimation.

This article is concerned with the power to detect the presence of genotype by environment interaction (G x E) in the case that both genes and environment feature as latent (i.e., unmeasured) variables. The power of the test proposed by Jinks and Fulker (1970), which is based on regressing the absolute difference between the scores of monozygotic twins on the sums of these scores, is compared to the power of an alternative test, which is based on Marginal Maximum Likelihood (MML). Simulation studies showed that generally the power of the MML-based test was greater than the power of the Jinks and Fulker test in detecting linear and curvilinear G x E interaction, regardless of whether the distribution of the data deviated significantly from normality. However, after a normalizing transformation, the Jinks and Fulker test performed slightly better. Some possible future extensions of the MML-based test are briefly discussed.

Biometry↗
PubMed2005

Use of sequence data generated in the Bayer Tru Gene genotyping assay to recognize and characterize non-subtype-b human immunodeficiency virus type 1 strains.

Human immunodeficiency virus type 1 (HIV-1) protease (PR) and reverse transcriptase (RT) gene sequences obtained during antiretroviral resistance testing with a commercial genotyping assay (Tru Gene; Bayer Corp.) were analyzed to assess the utility of these data for detecting and characterizing non-subtype-B HIV-1 strains. A total of 125 viral sequences obtained from patients believed to have acquired their HIV-1 infection in Africa were analyzed, of which 121 were determined to belong to non-B subtypes. Utilizing Tru Gene sequence data alone, 92 (76%) of these viruses could be subtyped by conventional phylogenetic analysis. The addition of supplemental RT sequence data enabled a further 28 (23.1%) viruses to be classified, while one (0.9%) sample could not be classified conclusively. Two internet-accessible databases that generate HIV-1 subtypes from PR and RT sequences (HIV-SEQ and Geno 2 Pheno) were also evaluated, and both achieved 88% concordance (106/120) with phylogenetic analysis. Non-subtype-B and B-subtype HIV-1 sequences could be readily discriminated by tallying silent polymorphisms listed on the Tru Gene research report. The mean number of silent polymorphisms in the non-B HIV-1 sequences identified in this study was 58.3 (95% confidence interval [CI], 41.1 to 75.5), compared with 20.7 (95% CI, 9.9 to 31.5) for the four subtype B viruses in the study cohort and 118 case-matched B-subtype controls. Sequence data generated in the Tru Gene HIV-1 genotyping assay could, therefore, provide a ready means of tracking the prevalence and identity of non-B subtypes in HIV-1-infected populations undergoing routine antiretroviral resistance testing.

Algorithms↗
PubMed2000

Pedigree tests of transmission disequilibrium.

High-resolution mapping is essential for the positional cloning of complex disease genes. In outbred populations, linkage disequilibrium is expected to extend for short distances and could provide a powerful fine-mapping tool. Current family-based association tests use nuclear family members to define allelic transmission and controls, but ignore other types of relatives. Here we construct a general approach for scoring allelic transmission that accommodates families of any size and uses all available genotypic information. Family data allows for the construction of an expected genotype for every non-founder, and orthogonal deviates from this expectation are a measure of allelic transmission. These allelic transmission scores can be used to extend previously described tests of linkage disequilibrium for dichotomous or quantitative traits. Some of these tests are illustrated, together with a permutation framework for estimating exact significance levels. Simulation studies are used to investigate power and error rates of the approach. As a practical application, the method is used to investigate the relationship between circulating angiotensin-1 converting enzyme (ACE) levels and polymorphisms in the ACE gene using previously published data.

Alleles↗
PubMed1997

Analysis of histopathological manifestations of chronic hepatitis C virus infection with respect to virus genotype.

Hepatitis C virus (HCV) causes acute and often chronic hepatitis. On the basis of variations in nucleotide sequence, at least six genotypes and several subtypes have been identified. Histopathologically, chronic HCV infection is characterized by relatively mild hepatic inflammatory activity and a low degree of fibrosis, but hepatic lesions might be accompanied by bile duct damage, intraportal lymphoid aggregates, steatosis, or a combination of these manifestations. The histopathological lesions thus appear quite heterogeneous. To address the question of whether distinct histopathological manifestations are related to particular genotypes of HCV, 90 patients with chronic HCV infection were analyzed regarding histopathological features, biochemical liver parameters, demographic data, and virus genotype. The results revealed a significantly higher prevalence of both steatosis and bile duct lesions among patients infected by HCV type 3a compared to patients infected by types 1a or 1b. Furthermore, the data suggest interrelationships between virus genotype, patient's age, and a history of intravenous drug abuse. However, none of the histopathological manifestations were found to be related to a history of drug abuse. The data further corroborate the relationship of HCV type 1b infection to age, duration of disease, and the degree of fibrosis, respectively. Irrespective of HCV genotype, elevated serum ALT activity was shown to be associated with pronounced inflammatory activity or pronounced steatosis as well. Thus, the current data support the hypothesis that distinct genotypes of HCV appear to be associated with distinct manifestations of disease.

Adult↗
PubMed1986

HLA-DR4 in insulin-dependent diabetic parents and their diabetic offspring: a clue to dominant inheritance.

Insulin-dependent diabetes mellitus (IDDM) susceptibility determinants are known to be associated with both HLA-DR3 and -DR4. We monitored the inheritance of HLA-DR alleles in 37 families in which IDDM affected one parent and at least one offspring in order to try to learn more about the modes of inheritance of IDDM determinants. Ninety-seven insulin-dependent diabetics whose parents did not have diabetes and 158 nondiabetics were used as control groups for estimates of DR allele frequencies in the overall diabetic and general populations. The proportion of diabetic parents who transmitted DR4 to diabetic offspring (78%) was significantly higher (P less than 0.001) than the gene frequency of DR4 in the overall diabetic population (43%). The proportion of nondiabetic parents who transmitted DR4 to diabetic offspring (22%) was not significantly different from the gene frequency of DR4 in the nondiabetic population (16%), but it was significantly lower (P less than 0.05) than the gene frequency in the overall IDDM population. These proportions suggest that inheritance of the DR4-associated IDDM susceptibility determinant is not recessive, because in recessive inheritance expression of a trait depends on each parent contributing a susceptibility determinant. The proportions of diabetic and nondiabetic parents who transmitted the DR allele associated with the susceptibility determinant would then equal one another. The transmission of predominantly DR4 from affected parents to affected offspring suggests that susceptibility to IDDM is inherited primarily via a single dose of a potent determinant associated with DR4, as in dominant inheritance. When DR3 was transmitted at all it was usually by the nondiabetic parent. Only 8% of diabetic parents transmitted DR3 but 35% of nondiabetic parents transmitted DR3. The proportion of nondiabetic parents who transmitted DR3 was similar to the gene frequency of DR3 in the overall diabetic population (29%), but it was significantly higher than the gene frequency of DR3 in the nondiabetic population (15%; P less than 0.005). The percentage of diabetic offspring with the genotype DR3DR4 (35%) was identical to the percentage of individuals in the overall IDDM population with this genotype (35%). Numerous population data indicate that the DR3DR4 genotype carries a higher relative risk for IDDM than any other genotype, which suggests synergism between the DR3- and DR4-associated determinants. The family data reported here support this synergism but suggest that the DR4-associated determinant can give substantial susceptibility independent of the DR3-associated determinant and that the DR3-associated determinant is often expressed as enhancing susceptibility in the presence of the dominant DR4- associated determinant.

Adolescent↗
PubMed1996

Mutation analysis in hereditary hemochromatosis.

The DNA of 147 patients of European origin clinically diagnosed with idiopathic hemochromatosis and 193 controls was examined for mutations of the HLA-H gene at nt 845 and nt 187. One hundred twenty-one (82.3%) of the hemochromatosis patients were homozygous and 10 (6.8%) heterozygous for the 845A (C282Y) mutation. All of the homozygous patients were also homozygous for nt 187C, and all 845A heterozygotes had at least one copy of 187C. Thus, the nt 845 and nt 187 mutations were in complete linkage disequilibrium; nt 187 was a C on all chromosomes with the 845A mutation. Eight of the 10 heterozygotes for 845A were heterozygous for 187G(H63D). The excess of heterozygotes at both nt 187 and nt 845 suggested either the presence of as yet undiscovered mutations existing in trans with 845A and in linkage disequilibrium with 187G, or that the 187G itself is a deleterious mutation, which in concert with the 845A can give rise to hemochromatosis. None of the 193 normal controls were homozygous for 845A and 29/193 (15%) were heterozygous for 845A. Although 47/193 (24.3%) of normal controls were heterozygous for the 187G mutation only two of these carried the 845A mutation. If the 187G mutation complemented the 845A mutation with high penetrance in causing hemochromatosis, then the population frequency of the two genes would require that a high proportion of patients with hemochromatosis be heterozygous for 845A and 187G. Instead, the frequency of homozygotes for the 845A mutation was much higher than that of the 845A/187G genotype. Based on our data, the penetrance of the 845A/187G genotype is only 1.5% and based on the data of Feder et al. only 0.5%. In contrast, the penetrance of the homozygous 845A/845A genotype seems to be very high. Thus, screening for this genotype should be very useful.

Alleles↗