Nallur B. Ramachandra

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.

Genome-wide copy number scan identifies disruption of PCDH11X in developmental dyslexia

Developmental dyslexia (DD) is a complex heritable disorder with unexpected difficulty in learning to read and spell despite adequate intelligence, education, environment, and normal senses. We performed a whole genome copy number variations (CNV) scan on 11 dyslexic families consisting of 14 dyslexic subjects and 24 non dyslexic members using 1.8 million combined SNP and CNV markers. We found CNVs affecting protocadherin genes in six dyslexics from three families, while none among the non‐dyslexic control members showed any CNV in protocadherins. We identified duplications in five cases and a deletion in one case in Xq21.3 region bearing PCDH11X. Unequal recombination between the X‐transposed region (XTR) of Yp11.2 and the X chromosome might be causing these structural changes. PCDH11X, expressed in brain is implicated in cell–cell communication, verbal ability, cerebral asymmetry, and dendritic synaptic plasticity, may be regarded as a new candidate gene for dyslexia.

Analysis of genetic variants of dyslexia candidate genes KIAA0319 and DCDC2 in Indian population

Developmental dyslexia (DD) is a heritable, complex genetic disorder associated with impairment in reading and writing skills despite having normal intellectual ability and appropriate educational opportunities. Chromosome 6p23-21.3 at DYX2 locus has showed the most consistent evidence of linkage for DD and two susceptible genes KIAA0319 and DCDC2 for DD at DYX2 locus showed significant association. Specific candidate gene-association studies have identified variants, risk haplotypes and microsatellites of KIAA0319 and DCDC2 correlated with wide range of reading-related traits. In this study, we used a case–control approach for analyzing single-nucleotide polymorphisms (SNPs) in KIAA0319 and DCDC2. Our study demonstrated the association of DD with SNP rs4504469 of KIAA0319 and not with any SNPs of DCDC2.

Prevalence of congenital heart diseases in Mysore

Background: Prevalence studies on Congenital heart Diseases (CHDs) have been done several times world wide and such studies are very limited in Indian populations. A few earlier studies in India have reported an increased prevalence of CHDs ranging from 2.25 to 50.89 per 1000 live births. Aims and Objective: To study the prevalence of congenital heart diseases in Indian population. Materials and Methods: Data on the prevalence of CHDs were collected and analyzed from the three major hospitals of Mysore, Cheluvamba Hospital, CSI Holdsworth Memorial Hospital and J.S.S Hospital from the year 2000 to 2004. Results: The prevalence of CHDs for five years in Mysore hospitals ranges from 6.6 to 13.06 per 1000 live births. The most frequent type of CHD was found to be VSD (40.47%) followed by ASD (19.06%), TOF (13.38%) and PDA (9.53%). It is clear that the maximum CHDs were detected in the first year of life when compared to the later years of life. The prevalence of CHDs in Mysore is increasing from 2000 to 2004 which might be due to the improvement of diagnosis, attention or awareness among the medical authorities on the disease. Conclusion: The prevalence of CHDs in Mysore is not very high as reported in other parts of the country, however; it is an important disease which needs an immediate medical attention.

Serum levels of IL-10, IL-17F and IL-33 in patients with asthma: a case–control study

Abstract Objectives: The development of inflammation in asthma involves an intricate network of cytokines that recruit and activate numerous immune cells. This study was aimed to compare serum levels of IL-10, IL-17F, and IL-33 in asthmatic patients and non-asthmatic controls and correlate cytokine levels to asthma severity and various clinical, spirometric, and laboratory variables. Methods: Using ELISA, serum levels of IL-10, IL-17F, and IL-33 were evaluated in 44 asthmatics (14 mild persistent, 15 moderate persistent, and 15 severe persistent) and 44 controls. Results: This is one of the first reports showing a significant difference in serum levels of asthma-associated cytokines, anti-inflammatory IL-10, and pro-inflammatory IL-17F and IL-33, in the same subset of asthmatic patients. Our results showed diminished level of IL-10 and elevated levels of IL-17F and IL-33 in asthmatics than in controls (p < 0.001). Assessment of cytokine levels between subjects of different gender, age group, and BMI showed non-significant differences. Correlation analysis of cytokine levels to clinical variables showed that IL-17F is associated negatively to FVC % predicted (forced vital capacity) and FEV1% predicted (forced expiratory volume in one second) and positively to number of allergens sensitized and FEV1 reversibility. A strong negative correlation was found between IL-10 and IL-33 levels (p = 0.001). Conclusions: Negative correlation between IL-10 and IL-33 levels may reflect a converse relationship between anti-inflammatory and pro-inflammatory cytokines in an individually balanced pattern. The association between IL-17F level and asthmatic phenotypes such as reduced FVC and FEV1, higher degree of sensitization, and post-bronchodilator reversibility needs further assessments.

Family-based genome-wide copy number scan identifies five new genes of dyslexia involved in dendritic spinal plasticity

Genome-wide screening for copy number variations (CNVs) in ten Indian dyslexic families revealed the presence of five de novo CNVs in regions harboring GABARAP, NEGR1, ACCN1, DCDC5, and one in already known candidate gene CNTNAP2. These genes are located on regions of chromosomes 17p13.1, 1p31.1, 17q11.21, 11p14.1 and 7q35, respectively, and are implicated in learning, cognition and memory processes through dendritic spinal plasticity, though not formally associated with dyslexia. Molecular network analysis of these and other dyslexia-related module genes suggests them to be associated with synaptic transmission, axon guidance and cell adhesion. Thus, we suggest that dyslexia may also be caused by neuronal disconnection in addition to the earlier view that it is due to neuronal migrational disorder.

An examination of candidate gene SNPs for dyslexia in an Indian sample.

Developmental dyslexia (DD) is a complex neuro-genetic disorder associated with difficulty in learning to read despite adequate intelligence and educational opportunities. Studies in different populations have established associations between DD and single nucleotide polymorphisms (SNPs) in a number of candidate genes, including DYX1C1, KIAA0319 and DCDC2. In an ongoing DD study in India, we screened twenty SNPs located within the coding region of these three candidate genes by massARRAY technique. At this point, there is no statistical evidence of association between the allelic variation in the three candidate genes and DD in our sample, although there might be some promising leads for future research that should involve a large and a better characterized sample.

Evolutionary experimentation through hybridization under laboratory condition in Drosophila : Evidence for Recombinational Speciation

BackgroundDrosophila nasuta nasuta (2n = 8) and Drosophila nasuta albomicans (2n = 6) are a pair of sibling allopatric chromosomal cross-fertile races of the nasuta subgroup of immigrans species group of Drosophila. Interracial hybridization between these two races has given rise to new karyotypic strains called Cytorace 1 and Cytorace 2 (first phase). Further hybridization between Thailand strain of D. n. albomicans and D. n. nasuta of Coorg strain has resulted in the evolution of two more Cytoraces, namely Cytorace 3 and Cytorace 4 (second phase). The third phase Cytoraces (Cytorace 5 to Cytorace 16) have evolved through interracial hybridization among first, second phase Cytoraces along with parental races. Each of these Cytoraces is composed of recombined genomes of the parental races. Here, we have made an attempt to systematically assess the impact of hybridization on karyotypes, morphometric and life history traits in all 16 Cytoraces.ResultsThe results reveal that in most cases, the newly evolved Cytoraces, with different chromosome constitutions, exhibit decreased body size, better fitness and live longer than their parents. Particularly, Cytorace 5, 6 and 8 have evolved with very much higher range values of quantitative traits than the parents and other Cytoraces, which suggests the role of transgressive segregation in the evolution of these Cytoraces.ConclusionThus, the rapid divergence recorded in the chromosomes, karyotypes, body size and fitness traits of Cytoraces exhibit the early event of recombinational raciation / speciation in the evolution of the Cytoraces under laboratory conditions.

De novo isochromosome 18p in a female dysmorphic child

Isochromosome 18p results in tetrasomy 18p. Most of the i(18p) cases reported so far in the literature are sporadic due tode novo formation, while familial and mosaic cases are infrequent. It is a rare chromosomal abnormality, occurring once in every 140 000 livebirths, affecting males and females equally. In the present investigation, we report ade novo i(18p) in a female dysmorphic child. The small metacentric marker chromosome was confirmed as i(18p) in the proband by cytogenetic and FISH analysis [47,XX + i(18p)]. Cytogenetic investigations in the family members revealed normal chromosome numbers, indicating the case as ade novo event of i(1 8p) formation. It could be due to the somewhat advanced maternal age (32 years) and/or expression of recessive genes in the proband, who is the progeny of consanguineous marriage, which could have led to misdivision and nondisjunction of chromosome 18 in meiosis I, followed by failure in the chromatid separation of 18p in meiosis II and by inverted duplication.

Incipient sexual isolation in the nasuta-albomicans complex of Drosophila: mating preference in male-, female- and multiple-choice mating experiments

Interracial divergence is an important facet of speciation. Thenasuta-albomicans complex ofDrosophila with sixteen morphologically identical, karyotypically different but cross-fertile races is an excellent system to study a few dimensions of raciation.Drosophila nasuta nasuta, Drosophila nasuta albomicans, Cytorace 1, Cytorace 2, Cytorace 3 and Cytorace 4 of this subgroup have been subjected to male-, female- and multiple-choice mating experiments. Out of 8456 crosses conducted, 7185 had successful matings. The overall impression is that mating is far from random amongst these six closely related races of thenasuta-albomicans complex. The males ofD. n. albomicans, Cytorace 1 and Cytorace 4 in male-choice, the females of Cytorace 1 and Cytorace 2 in female-choice, and the males and females ofD. n. nasuta, D. n. albomicans, Cytorace 1 and Cytorace 4 against the males and females of Cytorace 2 in multiple-choice experiments, had significantly more homogamic matings than expected. Thus in this study of evolutionary experimentation on raciation under laboratory conditions, we have documented the initiation of preference for con-specific matings among closely related and independently evolving members of thenasuta-albomicans complex ofDrosophila.