Suttur S. Malini

Influence of advanced age of maternal grandmothers on Down syndrome

BackgroundDown syndrome (DS) is the most common chromosomal anomaly associated with mental retardation. This is due to the occurrence of free trisomy 21 (92–95%), mosaic trisomy 21 (2–4%) and translocation (3–4%). Advanced maternal age is a well documented risk factor for maternal meiotic nondisjunction. In India three children with DS are born every hour and more DS children are given birth to by young age mothers than by advanced age mothers. Therefore, detailed analysis of the families with DS is needed to find out other possible causative factors for nondisjunction.MethodsWe investigated 69 families of cytogenetically confirmed DS children and constructed pedigrees of these families. We also studied 200 randomly selected families belonging to different religions as controls. Statistical analysis was carried out using logistic regression.ResultsOut of the 69 DS cases studied, 67 were free trisomy 21, two cases were mosaic trisomy 21 and there were none with translocation. The number of DS births was greater for the young age mothers compared with the advanced age mothers. It has also been recorded that young age mothers (18 to 29 years) born to their mothers at the age 30 years and above produced as high as 91.3% of children with DS. The logistic regression of case- control study of DS children revealed that the odds ratio of age of grandmother was significant when all the four variables were used once at a time. However, the effect of age of mother and father was smaller than the effect of age of maternal grandmother. Therefore, for every year of advancement of age of the maternal grandmother, the risk (odds) of birth of DS baby increases by 30%.ConclusionBesides the known risk factors, mothers age, fathers age, the age of the maternal grandmother at the time of birth of the mother is a risk factor for the occurrence of Down syndrome.

Prevalence of Childhood Obesity in School Children from Rural and Urban Areas in Mysore, Karnataka, India

Abstract Prevalence studies on obesity in school children has been carried out extensively worldwide but such explorations are very limited in Indian populations, especially a comparative account between rural and urban areas. Very few earlier investigations in India have reported an increased prevalence of childhood obesity ranging from 5.5 % to 17%. This study was designed to know the prevalence of childhood obesity in school children from rural and urban areas in Mysore population. Data on the prevalence of obesity in children were collected and analyzed from three and four major schools from urban and rural areas of Mysore district respectively. The prevalence of childhood obesity in Mysore is not very high as compared to other reports from different regions of the country. However, it is an important multifactorial condition which needs immediate medical attention to stop the march of healthy children towards chronic disorders.

A Journey on Y Chromosomal Genes and Male Infertility

Abstract In the course of evolution Y chromosome has acquired an important role in sex determination owing to the differentiation of the SRY gene from its X homologue. Apart from the functionally specialized SRY gene, the Y chromosome harbors several genes responsible for normal fertility. Three different spermatogenic loci namely AZFa, AZFb and AZFc located in the long arm of Y chromosome (Yq) has the vital role in regulating normal spermatogenesis. A microdeletion occurring in any of these regions is attributed to spermatogenic failure leading to infertility in men. Genetic cause of male infertility is found to be 10-15% and the outcome is diverse ranging from no germ cells (Sertoli Cell Only syndrome) to hypospermatogenesis. Genes arrayed in the AZFc region have testis specific expression and deletion of the AZFc region is most common among the Y micro-deletions in men with azoospermia condition. Among the candidate genes ofthe AZFc region the deletion involving DAZ is considered to be the frequent cause leading to azoospermia. The mechanism of micro-deletion is found to be the same in case of AZFa and AZFc region. Among these two loci homologous recombination of flanking, identical sequences leads to micro-deletion. But in case of AZFb region the proximal and distal breakpoints does not exhibit sequence homology although interspersed repeated sequences exist in proximity to the break points.

Role of phenylthiocarbamide as a genetic marker in predicting the predisposition of disease traits in humans.

The main objective of this study is to find out the genetic variation and predisposition of overweight/obese, smoking/alcoholism and thyroid disease traits among tasters and non-tasters in Mysore population, South India. Bitter-taste perception for phenylthiocarbamide (PTC) is a classically variable trait both within and between human populations. Many studies have reported that in world population, approximately 30% of them are PTC non-tasters and 70% are tasters. This investigation was conducted during the year 2009-2010 involving a total 1352 study subjects and divided into three different groups, considering the age ranging from 13 to 50 years. Phenylthiocarbamide taste sensitivity was measured by administering a freshly prepared 0.025% of phenylthiocarbamide solution using the Harris and Kalmus method with a slight modification and the results were recorded. In the first group of 100 obese/overweight children, 28% are taster and 72% are non-taster and among 100 control group 67% are tasters and 43% are non-tasters. In second group, out of 1152 individuals 710 (61.63%) are tasters and 442 (38.37%) are non-tasters including both males and females. In the third group, out of each 100 thyroid patients and the control group, tasters are significantly more frequent (61.41%) than the non-tasters (38.58%) in the control group, but a higher proportion of non-tasters are recorded among individuals with thyroid problems (68%) compared to tasters (32%). There is a significant higher incidence of PTC tasters than non-tasters among general population in this study. As phenotypic variation in PTC sensitivity is genetic in origin, this may represent a surrogate risk factor for the development of multifactorial disease and disorders.

An Overview of Genetic and Molecular Factors Responsible for Recurrent Pregnancy Loss

Abstract Recurrent pregnancy loss usually results from disorders that cause intrauterine fetal damage, such as maternal or paternal chromosomal abnormalities. About 15 to 20 percent of all recognized pregnancies end in a first-trimester spontaneous abortion. Parents who are carriers of structural abnormalities have a higher risk of miscarriage because of the aberrations in genetic information may not segregate properly into the reproductive cells. This may be due to translocations, inversions, deletions, and duplications causing pregnancy loss. It is believed that between 3 and 5 percent of recurrent miscarriages are due to genetic factors, about 7 percent are caused by chromosome defects, 15 percent to hormonal defects, and 10 to 15 percent to anatomical defects. The most common cause of early pregnancy losses are chromosomal abnormalities that occur by chance, except in the case of parental chromosomal rearrangements and are not under any controllable influences. This review focuses on the genetic and molecular abnormalities that may contribute to this clinical problem and delineates strategies for genetic evaluation and clinical management in subsequent pregnancies

Possible risk factors for Down syndrome and sex chromosomal aneuploidy in Mysore, South India.

BACKGROUND: Down syndrome (DS) and sex chromosomal aneuploidy (SA) are common chromosomal anomalies causing congenital malformations and mental retardation in humans. The well-established risk factor, advanced maternal age, was not found in many of the DS and SA cases in India, while the other possible risk factors have not been well studied. In view of this, the present study has been made. MATERIALS AND METHODS: During the last 5 years, 150 clinically suspected DS and 25 SA cases were referred to our laboratory for chromosome investigation from major hospitals of Mysore city. Chromosome preparations were made from these patients after informed consent was obtained. Well-spread G-banded metaphase plates were analyzed by automated LEICA KARYO software. Two hundred and 100 randomly selected families belonging to different religions were used as controls for the DS and SA cases, respectively. Statistical analysis was carried out using logistic regression RESULTS: Out of the 150 cases of DS, 122 had free trisomy 21, two were mosaic trisomy 21, and one had translocation. Logistic regression of case-control study of DS children revealed that the odds ratio of uncle-niece marriages, or second cousin marriages, or parents lived in rural region, or exposure of the parents to chemicals, or parents education status, or habits (tobacco/ alcohol used) of father, or mother not undergone prenatal scanning, or mothers with previous abortions were significant when all the variables of that category were used one at a time. Exposure of the parents to chemicals, parents’ educational status, habits (tobacco/alcohol use) of the father, mother not undergone prenatal scanning, and history of previous abortions were significant when all the variables of that category were used one at a time. Similarly, except for consanguinity, history of previous abortions, and mother not undergone prenatal scanning, all other factors showed significant odds ratios in SA cases. CONCLUSION: Besides the known risk factors, consanguinity, region (rural/urban) of residence of parents, exposure of parents to chemicals, educational status of parents, habits of father, prenatal scanning, and reproductive performance of mother are possible risk factors for chromosomal aneuploidy.

Impact of Y chromosome AZFc subdeletion shows lower risk of fertility impairment in Siddi tribal men, Western Ghats, India

BackgroundIndia is characterized by the presence of a large number of endogamous castes, tribes and religions, having second largest concentration of tribal population in the World with differed genetic ethnicity, lifestyle and environmental habitat from those of mainstream population. Lack of data is constraint when it comes to tracking the tribal population health status, specifically reproductive health aspects by experimental approaches. The male fertility impairment depends on Y chromosome azoospermia factor c (AZFc) subdeletions, which varies highly in different geographical populations and in an Indian admixed population the frequency and effect of deletion on fertility is relatively poorly documented. Therefore, the current study has been initiated to enumerate and characterize the strength of association between Yq11 AZFc subdeletions and fertility impairment among Siddi tribal men of Western Ghats, India.MethodsHere, using predesigned performa we collected personal as well as familial information of 200 volunteered male subjects and grouped them into: (i) 104 married individuals with proven fertility, and (ii) 96 unmarried men with unknown fertility status. Quantification of reproductive hormones such as follicle stimulating hormone (FSH), leutinizing hormone (LH) and testosterone were studied. Oxidative stress markers like total antioxidant capacity (TAC) and super oxide dismutase (SOD) along with analysis of five sequence tagged site (STS) hotspot markers were employed for mapping of Y chromosome AZFc subdeletions. Statistical analyses were performed using SPSS software.ResultsHormonal analysis and estimation of oxidative stress markers showed normal values with no significant differences between two subgroups. However, the Y chromosome AZFc subdeletion mapping revealed evident results as an individual displayed absence of STS sY1191 marker indicating b2/b3 deletion, whereas rest of the subjects exhibited no deletion for all the five STS markers. While, the individual has fathered two children, at this point it is difficult to draw a causal link between the observed deletion and its effect on fertility.ConclusionThus, our current study suggests that the association between AZFc subdeletions with its effect on infertility varies highly in this study cohort compared to other Indian ethnic groups, exhibiting lower risk factor and non-association reaching insignificance among Siddi tribal men.

Evolution of phenylthiocarbamide taster trait in Mysore, South India.

BACKGROUND: The ability to taste phenylthiocarbamide (PTC), a bitter chemical has long been known to be a heritable trait, which is being widely used for both genetic and anthropological studies. The frequency of taster and non-taster allele is found to vary in different populations. AIMS AND OBJECTIVE: To investigate the frequency of taster trait in Mysore, South India. MATERIALS AND METHODS: The present investigation was conducted in Mysore, South India during 2002 - 2003. About 3282 subjects irrespective of age, sex, religion, food habits, socio-economic status were randomly selected from various parts of the city and a total of 180 families, which included Christian (50), Hindu (61) and Muslim (69) were screened from different localities of the city. Harris and Kalmus method was used to assess the PTC taster and nontaster phenotype. RESULTS: It was found that tasters were significantly more frequent than nontasters in all the four categories. The incidence of tasters was more in unbiased category (85%) and less in Muslim category (58%). Investigations on PTC tasting in the families of three different religious groups revealed that the tasters were significantly more frequent than nontasters. It was also found that heterozygous father or mother for the taster genes with nontaster partner had taster and nontaster progenies in the ratio 1.0: 1.54 indicating the deviation in the segregation pattern of test cross. CONCLUSION: In Mysore, tasters are more frequent than nontasters. Variation in the frequency of nontaster allele in the religious groups could be due to inbreeding.

Young Mothers Produce More Chromosomal Syndrome Babies in Mysore, South India

Abstract Chromosomal syndromes contribute significantly to reproductive failure, birth defects, mental retardation, delayed puberty, and hermaphrodites in humans. It has been estimated that at least 5% of all human conceptions are aneuploids, most of them resulting in pregnancy loss. The well-established factor to produce babies with chromosomal syndromes is advanced age of mothers. However, in India, more of young mothers give birth to babies with chromosomal syndromes. The present study has been attempted to investigate the possible causes. A total of 175 children with chromosomal aneuploidy and 300 controls were screened for cytogenetic investigation from major hospitals of Mysore city. Genetic register was established, pedigree was constructed and degree of consanguinity was studied for the cases where parental consanguinity was evident. Cytogenetic and statistical analysis were carried out using logistic regression. Logistic regression of case-control study of babies with chromosomal aneuploidy revealed that the odds ratio was significant for advanced father and maternal grandmother’s age when all the variables were used together. The effect of age of father and age of maternal grandmother were increased in odds by 16% and 46% per extra year respectively. Along with the established risk factors like advanced age of parents, maternal grandmother’s age is also the potential possible risk factor for the manifestation of babies with chromosomal aneuploidy in young mothers.

High incidence of sperm dysfunction in a varicocele infertile man: case report

Abstract Studies indicate abnormal semen indicators among varicocele infertile men can be reversed to normal status after surgical repair. While semen indicators and DNA damage of sperms are reported frequently, sperm function tests are rarely performed to assess the functional status of sperms among these individuals. We report a 35-year-old male with 4 years of primary infertility who otherwise has a normal sexual life. Various analyses performed revealed the interplay of multiple abnormalities leading to the observed phenotype. The individual was diagnosed with severe sperm defects, bilateral varicocele (grade II) and endocrinopathy. The percentage of functionally normal sperms were found to be 24% for hypo-osmotic swelling, 28% for acrosome reaction and 21% for nuclear chromatin decondensation test. Cytogenetic analyses showed normal karyotype and sequence-tagged-site markers based PCR showed no deletions involving key candidate genes of the Y chromosome. A thorough investigation of infertile subjects and simple diagnostic tests are essential to detect the treatable defects, in general as well as severe infertile cases, which can improve the chances of normal conception or the success rates of in - vitro fertilization and intracytoplasmic sperm injection.