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ABSTRACT Objective: The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. Materials and methods: The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years' duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. Results: Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. Conclusion: Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients.
Subject(s)
Humans , Aldehyde Reductase/genetics , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Diabetic Nephropathies/complications , Diabetic Nephropathies/genetics , Case-Control Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Alleles , Gene Frequency , GenotypeABSTRACT
O recente desenvolvimento da biologia molecular tem aberto a possibilidade de identificar genes importantes e utilizar a variação genômica no melhoramento genético. Os marcadores moleculares baseados em DNA atuam como ferramentas versáteis e podem ser utilizados em diferentes estudos. Desde o seu desenvolvimento, os marcadores moleculares estão sendo modificados constantemente para melhorar sua empregabilidade e trazer a possibilidade de automação do processo em análises genômicas. A descoberta da reação em cadeia da polimerase (PCR) foi um marco nesse esforço e diversos marcadores surgiram a partir do desenvolvimento da PCR. Nessa revisão, diferentes marcadores moleculares baseados em DNA desenvolvidos durante as últimas décadas foram abordados, no qual auxiliará na compreenssão das diferentes classes de marcadores genéticos existentes e suas aplicações na seleção de genótipos superiores nos programas de melhoramento genético de bovinos.
The recent development in molecular biology has opened the possibility of identifying major genes and using genomic variation in breeding programs. DNA-based molecular markers have acted as versatile tools and can be used in different studies. Since their development, molecular markers are constantly being modified to improve their employment and bring the possibility of process automation in genomic analysis. The discovery of polymerase chain reaction (PCR) was a milestone in this effort and several markers have emerged from this technique. In this review, different DNA-based molecular markers developed during the last decades have been approached, which shall aid in the understanding of the different classes of genetic markers available and their application in the selection of superior genotypes in breeding cattle.
El reciente desarrollo de la biología molecular ha abierto la posibilidad de identificar genes importantes y utilizar la variación genómica en el mejoramiento genético. Los marcadores moleculares basados en ADN actúan como herramientas versátiles y pueden ser utilizados en diferentes estudios. Desde su desarrollo, los marcadores moleculares están siendo modificados constantemente para mejorar su empleabilidad y traer la posibilidad de automatización del proceso en análisis genómicas. El descubrimiento de la reacción en cadena de polimerasa (PCR) fue un hito en ese esfuerzo y diversos marcadores han surgido a partir del desarrollo de la PCR. En esa revisión, diferentes marcadores moleculares basados en ADN desarrollados durante las últimas décadas han sido abordados, lo que ayudará en la comprensión de las distintas clases de marcadores genéticos existentes y sus aplicaciones en la selección de genotipos superiores en los programas de mejoramiento genético de bovinos.
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Butyrylcholinesterase (BChE) is a plasma enzyme that catalyzes the hydrolysis of choline esters, including the muscle-relaxant succinylcholine and mivacurium. Patients who present sustained neuromuscular blockade after using succinylcholine usually carry BChE variants with reduced enzyme activity or an acquired BChE deficiency. We report here the molecular basis of the BCHE gene underlying the slow catabolism of succinylcholine in a patient who underwent endoscopic nasal surgery. We measured the enzyme activity of BChE and extracted genomic DNA in order to study the promoter region and all exons of the BCHE gene of the patient, her parents and siblings. PCR products were sequenced and compared with reference sequences from GenBank. We detected that the patient and one of her brothers have two homozygous mutations: nt1615 GCA > ACA (Ala539Thr), responsible for the K variant, and nt209 GAT > GGT (Asp70Gly), which produces the atypical variant A. Her parents and two of her brothers were found to be heterozygous for the AK allele, and another brother is homozygous for the normal allele. Sequence analysis of exon 1 including 5'UTR showed that the proband and her brother are homozygous for -116GG. The AK/AK genotype is considered the most frequent in hereditary hypocholinesterasemia (44 percent). This work demonstrates the importance of defining the phenotype and genotype of the BCHE gene in patients who are subjected to neuromuscular block by succinylcholine, because of the risk of prolonged neuromuscular paralysis.
Subject(s)
Humans , Butyrylcholinesterase , Polymorphism, Genetic , SuccinylcholineABSTRACT
Two active mutations (A 781 G and A 1575 G) in growth hormone (GH) gene, and their associations with litter size (LS), were investigated in both a high prolificacy (Matou, n = 182) and a low prolificacy breed (Boer, n = 352) by using the PCR-RFLP method. Superovulation experiments were designed in 57 dams, in order to evaluate the effect of different genotypes of the GH gene on superovulation response. Two genotypes (AA and AB, CC and CD) in each mutation were detected in these two goat breeds. Neither BB nor DD homozygous genotypes were observed. The genotypic frequencies of AB and CC were significantly higher than those of AA and CD. In the third parity, Matou dams with AB or CC genotypes had significantly larger litter sizes than those with AA and CD (p < 0.05). On combining the two loci, both Matou and Boer dams with ABCD genotype had the largest litter sizes when compared to the other genotypes (p < 0.05). When undergoing like superovulation treatments, a significantly higher number of corpora lutea and ova, with a lower incidence of ovarian cysts, were harvested in the AB and CC genotypes than in AA and CD. These results show that the two loci of GH gene are highly associated with abundant prolificacy and superovulation response in goat breeds.
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The applicability of mitochondrial nad6 sequences to studies of DNA and population variability in Lepidoptera was tested in four species of economically important moths and one of wild butterflies. The genetic information so obtained was compared to that of cox1 sequences for two species of Lepidoptera. nad6 primers appropriately amplified all the tested DNA targets, the generated data proving to be as informative and suitable in recovering population structures as that of cox1. The proposal is that, to obtain more robust results, this mitochondrial region can be complementarily used with other molecular sequences in studies of low level phylogeny and population genetics in Lepidoptera.
Subject(s)
Animals , DNA, Mitochondrial , Genetic Variation , Lepidoptera/genetics , Butterflies , Electron Transport Complex IV , Genetics, Population , Sequence Analysis, DNAABSTRACT
The aim of this work was to study the genetic diversity among flue-cured tobacco cultivars. RAPD and AFLP analyses were used to assess the genetic similarity among selected accessions of flue-cured tobacco. Seventy eight RAPD and 154 AFLP polymorphic bands were obtained and used to assess the genetic diversity among 28 tobacco accessions. The cultivar relationships were estimated through the cluster analysis (UPGMA) based on RAPD data and AFLP data. The accessions were grouped into three major clusters and these shared common ancestry clustered together.
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The heart fatty acid-binding protein (HFABP) gene was sequenced in parental animals of a F2 crossing of boars of the Brazilian native Piau breed with commercial sows (Landrace x Large White Pietrain). Primers used for PCR were designed to amplify four exons of the gene. The PCR products were sequenced and compared with the GenBank sequences. Differences between the generated sequences and the GenBank sequences were observed for both genetic groups. A total of 246 F2 animals were genotyped using the Hinf I restriction enzyme. Two genotypes were identified, 198 being animals HH and 48 Hh. The Hinf I SNP was significantly associated with weights of loin (bone-in) (P<0.05), jowl (P<0.05), sirloin (P<0.10), and kidneys (P<0.01). These results showed the potential of the H-FABP gene in marker-assisted selection programs for carcass traits in pigs.
O gene da proteína de ligação de ácidos graxos - coração foi seqüenciado em animais parentais de um cruzamento F2 entre varrões da raça nativa brasileira Piau e fêmeas comerciais (Landrace x Large White x Pietrain). Os primers utilizados na reação em cadeia da polimerase foram desenhados para amplificarem os quatro éxons do gene. Os fragmentos amplificados foram seqüenciados e comparados com a seqüência do gene depositada no GenBank. Foram observadas divergências entre as seqüências geradas e as do GenBank para ambos os grupos genéticos. Foram genotipados 246 animais F2 utilizando-se a enzima Hinf I. Dois genótipos foram identificados, sendo 198 animais HH e 48 animais Hh. O polimorfismo apresentou efeito sobre o peso total do carré (P<0,05), o peso da papada (P<0,05), o peso do filezinho (P<0,10) e o peso dos rins (P<0,01). Os resultados indicam que o gene da H-FABP apresenta potencial para aplicação em programas de seleção assistida por marcadores moleculares em suínos.
Subject(s)
Animals , Body Weight , Chromosome Mapping , Fatty Acid-Binding Proteins , Polymerase Chain Reaction , Polymorphism, Genetic , SwineABSTRACT
The ABO blood group is the most important blood group system in transfusion medicine and organ transplantation. To date, more than 160 ABO alleles have been identified by molecular investigation. Almost all ABO genotyping studies have been performed in blood donors and families and for investigation of ABO subgroups detected serologically. The aim of the present study was to perform ABO genotyping in patients with leukemia. Blood samples were collected from 108 Brazilian patients with chronic myeloid leukemia (N = 69), chronic lymphoid leukemia (N = 13), acute myeloid leukemia (N = 15), and acute lymphoid leukemia (N = 11). ABO genotyping was carried out using allele specific primer polymerase chain reaction followed by DNA sequencing. ABO*O01 was the most common allele found, followed by ABO*O22 and by ABO*A103. We identified 22 new ABO* variants in the coding region of the ABO gene in 25 individuals with leukemia (23.2%). The majority of ABO variants was detected in O alleles (15/60.0%). In 5 of 51 samples typed as blood group O (9.8%), we found non-deletional ABO*O alleles. Elucidation of the diversity of this gene in leukemia and in other diseases is important for the determination of the effect of changes in an amino acid residue on the specificity and activity of ABO glycosyltransferases and their function. In conclusion, this is the first report of a large number of patients with leukemia genotyped for ABO. The findings of this study indicate that there is a high level of recombinant activity in the ABO gene in leukemia patients, revealing new ABO variants.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged, 80 and over , Alleles , Genetic Variation , Leukemia/blood , ABO Blood-Group System/genetics , DNA , DNA Mutational Analysis , Genotype , Leukemia/classification , Polymerase Chain Reaction , Polymorphism, Genetic , ABO Blood-Group System/classificationABSTRACT
Background and objective Apolipoprotein E is a constituent of lipoproteins with considerable variation due to cysteine-arginine exchanges. We investigated the relationship between apo E gene polymorphism and the occurrence of coronary artery disease(CAD) in the older population of northern China. Methods The distribution of the HhaI polymorphisms of the apolipoprotein E gene was determined among 55 patients with CAD (CAD group), which was compared with that of 36 elderly subjects without CAD(control group). Results Genotype distributions at both sites (apo E gene 112-bp and 158-bp sites ) were different between the CAD and control groups. The CAD group had lower apolipoprotein Eε2frequencies than the control group (P＜0.05). Conclusion Individuals with apolipoprotein Eε2are likely to have a reduced risk of developing coronary artery disease as demonstrated by elderly subjects in Northern China.
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Ala100Thr has been suggested to be a Caucasian genetic marker on the FY*B allele. As the Brazilian population has arisen from miscegenation among Portuguese, Africans, and Indians, this mutation could possibly be found in Euro- and Afro-Brazilians, or in Brazilian Indians. Fifty-three related individuals and a random sample of 100 subjects from the Brazilian population were investigated using the polymerase chain reaction and four restriction fragment length polymorphisms. Confirming the working hypothesis, among the related individuals three Afro-Brazilians (two of them a mother and daughter) and a woman of Amerindian descent had the Ala100Thr mutation on the FY*B allele. Five non-related Euro-Brazilians also carried the mutation. All nine individuals presented the Fy(a-b+) phenotype. We conclude that the Ala100Thr mutation can occur in populations other than Caucasians and that this mutation does not affect Duffy expression on red blood cells. Gene frequencies for this allele in the non-related individuals were in agreement with those of other populations. The Duffy frequencies of two Amerindian tribes were also investigated.
Subject(s)
Humans , Male , Female , Genetic Variation , Receptors, Cell Surface , Mutation/genetics , Duffy Blood-Group System/genetics , Brazil , Phenotype , Genotype , American Indian or Alaska Native/genetics , Black People/genetics , White People/genetics , Genetic Markers , Polymorphism, Restriction Fragment Length , Polymerase Chain ReactionABSTRACT
@#ObjectiveTo investigate the relationship of the polymorphism of endothelial nitric oxide synthase (eNOS), the 27-bp variable number of tandem repeats (VNTR) in intron 4 with essential hypertension (EH) of the northern Han nationality in China.MethodsGenotypes, the level of plasma nitric oxide metabolites (NOx) and the activity of nitric oxide synthase (NOS) of 207 EH subjects and 231 healthy subjects were measured by polymerase chain-reaction (PCR).ResultsThe frequencies of ecNOS4a/a,ecNOS4b/a, and ecNOS4 b/b in the healthy group were 0.43%, 13.42% and 86.15% respectively. The frequency of the b allele was 92.86%, and the frequency of the a allele was 7.14%. While the frequencies of ecNOS4 a/a, ecNOS4 a/b,and ecNOS4 b/b in the EH group were 0.49%, 19.32% and 80.19% respectively. The frequency of the a allele in EH group (n=42, 10.15%) was significantly higher than that in the healthy group (n=33, 7.14%)(P<0.05). The plasma NOx level of the EH group was 70.04±14.68 mol/L, and significantly lower than that 84.09±27.27 mol/L in the healthy group (P<0.05). Similarly, both the plasma TNOS and iNOS activities of the EH group were 35.49±12.8 U/ml and 14.92±7.93 U/ml, and markedly lower than that 41.47±13.2 U/ml and 10.11±6.21U/ml in the healthy group (P<0.05). But the activities of eNOS in the EH group and healthy group were not significantly different (P>0.05).ConclusionThe variations of ecNOS4 gene locus may be responsible for the decrement of plasma NOx, both plasma NOx level and activity of NOS decreases in EH patients, so it may be a genetic susceptibility marker for EH of the Han nationality in China.
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Mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism is associated with longevity in the Japanese population, and the Mt5178A genotype may confer antiatherogenic advantages. Individuals with the Mt5178A genotype may be more resistant to adult-onset diseases, such as myocardial infarction, cerebrovascular diseases and type 2 diabetes, than those with the Mt5178C genotype. Moreover, Mt5178 C/A polymorphism has been reported to be associated with blood pressure, serum lipid levels, hematological parameters, intraocular pressure, serum protein fraction levels and serum electrolyte levels in healthy Japanese individuals. Differences in the influence of habitual drinking or habitual smoking on health status between the Mt5178C genotype and the Mt5178A genotype have been reported. The individual modification of drinking habits or smoking habits based on the genotyping of Mt5178 C/A may promote improved health and lead to the establishment of personalized prevention strategies for adult-onset diseases.
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Mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism is associated with longevity in the Japanese population, and the Mt5178A genotype may confer antiatherogenic advantages. Individuals with the Mt5178A genotype may be more resistant to adult-onset diseases, such as myocardial infarction, cerebrovascular diseases and type 2 diabetes, than those with the Mt5178C genotype. Moreover, Mt5178 C/A polymorphism has been reported to be associated with blood pressure, serum lipid levels, hematological parameters, intraocular pressure, serum protein fraction levels and serum electrolyte levels in healthy Japanese individuals. Differences in the influence of habitual drinking or habitual smoking on health status between the Mt5178C genotype and the Mt5178A genotype have been reported. The individual modification of drinking habits or smoking habits based on the genotyping of Mt5178 C/A may promote improved health and lead to the establishment of personalized prevention strategies for adult-onset diseases.
Subject(s)
Genotype , Longevity , DNA, MitochondrialABSTRACT
Objective To evaluate engraftment status of patients after allogeneic hematopoietic stem cell transplantation(Allo-HSCT) and prompt relapse of disease based on DNA polymorphism analysis technique.Methods Sixty-six cases were detected by DNA polymorphism analysis technique and 25 cases were monitored and analyzed dynamically during this period.Results After Allo-HSCT,48 patients obtained type of donors,but 13 patients did not; 5 patients showed mixed chimerism.Two cases of type of donors converted into mixed chimerism and 4 cases of mixed chimerism converted into type of donors after some time. The others' engraftment status did not change.Conclusion DNA polymorphism analysis technique can detect engraftment status of patients exactly, rapidly, which provides effective evidences of constitution for more clinical therapy projects.
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OBJECTIVE: We used nucleated erythrocytes in maternal blood for prenatal determination of the fetal gender as the preliminary experiment for the screening of fetal genetic status and the BclI DNA polymorphism in an attempt to clarify the origin of erythrocytes in maternal blood. METHODS: In seventeen pregnant women, venous blood was withdrawn and the nucleated erythrocytes were recovered by magnetic activated cell sorting (MACS) and immunostaining. After isolation of nucleated erythrocytes by micromanipulation, we performed nested PCR for amelogenin gene to identify the fetal gender and performed BclI DNA polymorphism to clarify the origin of erythrocytes. RESULTS: We could amplify the minute DNA in a single cell by primer extension preamplification and nested PCR of amelogenin gene in 94 (48.7%) cells and could identify the fetal gender by 58.8%. BclI DNA polymorphism revealed that the several cells, which did not reveal the specific band of Y chromosome in spite of the pregnancy of male fetuses, must be the cells from mother. CONCLUSION: Through this study, we could conclude that several nucleated erythrocytes in maternal blood circulation can originate from mother, therefore we must develop the new method to identify the nucleated erythrocyte of fetal origin. Considering that we must apply for the larger number of pregnant women to screen, the procedure was multi-step and complex. Therefore, we must design the new scheme to utilize the nucleated erythrocytes in maternal blood.
Subject(s)
Female , Humans , Male , Pregnancy , Amelogenin , Blood Circulation , DNA , Erythroblasts , Erythrocytes , Fetus , Mass Screening , Micromanipulation , Mothers , Polymerase Chain Reaction , Pregnant Women , Y ChromosomeABSTRACT
OBJECTIVES: The aging process affects responsiveness and other functions of endothelium and vascular smooth muscle cells, predisposing the old vessels to the development of atherosclerotic lesions. Endothelial nitric oxide synthase (ecNOS) gene polymorphisms were shown to affect the occurrence of acute myocardial infarction (AMI). We hypothesized that aging may affect the association between the ecNOS gene polymorphism and AMI. METHODS: We investigated the age-related distribution of the ecNOS gene a/b polymorphism in 121 male AMI patients and 206 age-matched healthy male controls. RESULTS: The aa, ab and bb genotypes were found in 1, 49 and 156 cases among the control subjects and 5, 23 and 93 cases among the AMI patients, respectively. There was a significant correlation between the ecNOS polymorphism and AMI (p +AD0- 0.045). When the correlation was analyzed by age, the significance remained only in the group below the age of 51 (p +AD0- 0.009). The proportion of smokers was increased in the young patients when compared to the old patients (p +AD0- 0.033), indicating that smoking also has greater effect on the younger population. The incidences of hypertension and diabetes mellitus, however, were similar in both populations. CONCLUSION: Our work provides the first evidence that links ecNOS polymorphism to the risk of AMI in relation to age. Young persons who smoke or have ecNOSaa genotype may have an increased risk of developing AMI. The functional as well as structural changes associated with aging in the vascular endothelium may mask the effect of the ecNOS polymorphism in the development of AMI in old persons.
Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Male , Age Distribution , Aging , Chi-Square Distribution , Comorbidity , Diabetes Mellitus/epidemiology , Endothelium, Vascular , Genotype , Hypertension/epidemiology , Korea/epidemiology , Middle Aged , Myocardial Infarction , Myocardial Infarction/epidemiology , Nitric Oxide Synthase , Nitric Oxide Synthase , Polymerase Chain Reaction , Risk Assessment , Statistics, NonparametricABSTRACT
BACKGROUND AND OBJECTIVE: The aging process affects the responsiveness and other functions of endothelium and vascular smooth muscle cells, predisposing the old vessels to the development of atherosclerotic lesions. Endothelial nitric oxide synthase (ecNOS) gene polymorphism was shown to affect the occurrence of acute myocardial infarction (AMI). We hypothesized that aging may affect the association between the ecNOS gene polymorphism and AMI. METHODS: We investigated the age-related distribution of the ecNOS gene a/b polymorphism in 121 male AMI patients and 206 age-matched healthy male controls. As a control, we also genotyped b-fibrinogen gene H1/H2 polymorphism in the same population. RESULTS: The aa, ab, and bb genotypes were found in 1, 49 and 156 cases among the control subjects and 5, 23 and 93 cases among the AMI patients, respectively. There was a significant association between the ecNOS polymorphism and AMI (p=0.045). When the correlation was analyzed by age, the significance remained only in the group below the age of 51 (p=0.009). The distribution of the b-fibrinogen gene H1/H2 alleles, however, was not found to be associated with development of AMI in both young (p=0.7400) and old (p=0.2160) population. CONCLUSION: Our results provide the first evidence that links ecNOS polymorphism to the risk of AMI in relation to age. Young persons who smoke or have ecNOS aa genotype may have an increased risk of developing AMI. The functional as well as structural changes associated with aging in the vascular endothelium may mask the effect of the ecNOS polymorphism in the development of AMI in old people.
Subject(s)
Humans , Male , Aging , Alleles , Endothelium , Endothelium, Vascular , Genotype , Masks , Muscle, Smooth, Vascular , Myocardial Infarction , Nitric Oxide Synthase , Nitric Oxide Synthase Type III , Smoke , SmokingABSTRACT
At present, because of enormous variety of mutations in hemophilia A, carrier detection and prenatal diagnosis by DNA analysis has been relied almost always on indirect detection using linkage analysis of DNA polymorphisms withim or near to the factor VIII gene. However, there is marked ethnic variation in the incidence of heterozygosity for a given DNA polymorphism. So it is very important to find out which DNA polymorphism pattern is useful in Korean families with hemophilia A for carrier detection and prenatal diagnosis. To identify the usefulness of DNA polymorphism in St14 VNTR locus for carrier detection and prenatal diagnosis of hemophilia A in Korean populations, we have analysed the DNA polymorphism in St14 VNTR locus in 80 Korean families with hemophilia A using polymerase chain reaction. We could identify 14 alleles in subjects studied, which ranges from 620 bp to 2830 bp. Expected heterozygosity rate, calculated from the allele frequencies, was 78.7%, and observed heterozygosity rate was 71.3% (57/80). Carrier detection was performed in 43 women from families informative with St14 VNTR : Seventeen women were diagnosed as non-carriers, 11 women as carriers. And 15 women were suspected to be carriers since they were from families of sporadic cases of hemophilia A. And prenatal diagnosis was done in 4 pregnant carrier women : noe fetus proved to be normal males, two fetuses to be normal females, and one to be a carrier. And five pregnant women, suspected to be carrier since they were from families of sporadic cases of hemophilia A, underwent prenatal diagnosis : One fetus was diagnosed as a normal mali, one as a normal female, two as possible carriers, and one as a possible affeted mali, whom the analysis of factor VIII level in fetal blood by cordocentesis revealed to be affected by hemophilia A. These data indicate that PCR-based analysis of St14 VNTR is very useful for the carrier detection and prenatal diagnosis of hemophilia A in Korea.
Subject(s)
Female , Humans , Male , Alleles , Cordocentesis , DNA , Factor VIII , Fetal Blood , Fetus , Gene Frequency , Hemophilia A , Incidence , Korea , Mali , Minisatellite Repeats , Polymerase Chain Reaction , Pregnant Women , Prenatal DiagnosisABSTRACT
Purposes : Down syndrome, the most common single cause of mental retardation, is usually due to meiotic nondisjunction leading to trisomy 21. In order to understand the mechanisms of meiotic nondisjunction including parental origin of an extrachromosome and the meiotic stage of nondisjunction, we have studied DNA polymorphisms at loci on the long arm of chromosome 21 in 36 families with free trisomy 21. METHODS: A total of 36 patients with Down syndrome who was cytogenetically diagnosed, and their parents were included in the study. The D21S11 locus was analysed using PCR follwed by denaturing polyacrylamide gel electrophoresis. RESULTS: The observed heterozygosity of D21S11 locus is 79.4% in the 104 unrelated Korean. Seven alleles with different sizes were observed. The parental origin of the extrachromosome 21 could be determined in 27 of 36 cases. The maternal origin was in 24 (88.9%) cases and paternal origin was in 3 cases (11.1%). Among informative cases, the meiotic error occurred at the first maternal meiosis in 9 (57.3%) cases and second meiosis in 7 (42.7%) of 16 cases. All paternal meiotic error occurred in the second meiosis. CONCLUSION: DNA haplotyping of the short tandem repeats markers can be very useful technique for molecular diagonosis and for determination of the parental origin of an extrachromosome 21 in Down syndrome. Nondisjunction of the maternal gamate is the main cause of trisomy 21, However, further studies with other polymorphic markers that locate at the centromere of chromosome 21 are needed in order to definitely determine the meiotic stage of nondisjunction in trisomy 21.