1. The document provides information about the educational and professional background of an individual, including degrees obtained from various institutions between 1973-2013 related to prenatal diagnosis, genetics, and rare syndromes. 2. It discusses various levels of genetics from DNA to populations and highlights key concepts like meiosis, mitosis, chromosomes, and mitochondrial DNA. 3. Genetics and genomics provides information at the cellular level about structure, expression, regulation and pathways/networks, but understanding the whole organism is still incomplete and requires integration of concepts from other fields like physics, chemistry and mathematics.

1. All India Institute of Medical Sciences
1973 - 1980
PRENATAL DIAGNOSIS CYTOGENETIC STATUS COUNSELLING
1980 - 1989
Banaras Hindu University
1989 Jawaharlal Nehru University
2010 - 2013
SHRI MATA VAISHNO DEVI
UNIVERSITY, SMVDU
GENETIC SUSCEPTIBILITY
MECHANISMS IN COMPLEX
DISEASES
RARE SYNDROMES

3. FROM MICROBE TO HUMANS – WE ARE UNIFIED WITH A COMMON LINK OF GENETIC
MATERIAL EVOLVED WITH TIME IN EVOLUTION – i.e., DEOXYRIBOSE NUCLEIC ACID -DNA
A COMMON THREAD UNIFYING BIOLOGY

4. Genetics is the transfer of biological information within a cell, an organism, or a
population. The Levels of Genetics: DNA, Genes, Chromosomes, Genomes, The
Cell, The Individual, A Family, The Population
23
46
23
ZYGOTE
MEIOSIS
MITOSIS
BLUE PRINT OF
AN INDIVIDUAL
WHAT ?
WHERE ?
HOW ?
AG T
T C A
Nucleus
Mitochondrial
100s of copies DNA
per cell
Chromatin
1014 cells in the
body
CELL
CELL & GENERATION
GENERATION
Mitochondrion
STRUCTURAL FEATURES
P M
TERMINOLOGIES
RFLPs
GENES
ALLELES/ SNPs
INS/DEL
NONCNV
ALLELES
SSRs
Gene Rich and Gene Poor Regions LOCI

5. HAS ITS OWN
LANGUAGE &
GEOGRAPHY
FULL OF
LANDSCAPES
LOT OF
PUZZLES
FULL OF HISTORY
ESTABLISHING
THE ROOTS
COMPARING WITH
OTHER SPECIES
POTENTIAL
FOR HUMAN
BENEFITS
SOMETHING TO
WORRY ABOUT

6. HUMAN GENOME
FULL OF HISTORY
MITOCHONDRIAL
MOTHER TO
DAUGHTERS AND
SONS
ESTABLISHING
THE ROOTS
Y - CHROMOSOMAL
FATHER TO
SONS

7. ANCESTRAL
II-LEVEL-DERIVED
MUTATION/VAR
I-LEVEL –DERIVED
MUTATION/VAR
I-LEVEL –DERIVED
MUTATION II-LEVELDERIVED
I-LEVEL -DERIVED
Y-CHROMOSOME
MITOCHONDRIA

8. Evolution of mitochondrial Haplogroups
Haplo-group 1 (ancestral)
Haplo-group 2
Haplo-group 3
Haplo-group 4
Haplo-group 6
Haplo-group 5
SNPs on mtDNA serve as markers for
detection of human evolution and diversity
Haplo-group 8
Haplo-group 7
Mutation + Variations in HVR regionsdivide the world population into different
“haplogroups”
Whole mitochondrial sequence is being used
to elucidate evolution & diversity

9. Biodiversity
&
Human Health
Disease Susceptibility

10. Genes - Simple and Complex Diseases
Whole Body
Which ?
Where ?
Controls
Behavior ?
Evolutionary
Which genes & why ?
Functionally
Different systems
& Organs
Cell types
Specific sets of
genes active
ubiquitous/tissue
specific, signals/
transporters etc
Implications
IMPRINTING; ANTICIPATION; ALLELIC HETEROGENEITY
LOCUS HETEROGENEITY, SPLICING ERRORS, PROMOTER
/ 5’ & 3’ UTR VARIATIONS; MICRO-RNA REGULATORS; POST-TRANSCRIPTIONAL
& POST-TRANSLATIONAL MODIFICATIONS; EPIGENETIC CONTROLS; SELECTION
PRESSURE-GENETIC DRIFT

11. GENOME SCREENS AND GENES INVOLVED
 Hypothesis Independent
Approach to find out T2DLinked chromosomal regions
And identify putative, causative
Genetic variants:





2q37.3-CAPN10,
6q22-q23-ENPP1,
20q13.12-HNF4A,
4p16.1-WFS1
12q13-ADC; etc

12. HYPOTHESIS INDEPENDENT- GENOME-WIDE ASSOCIATION STUDIES
TCF7L2, SLC30A8, HHEX, CDKAL1
IGF2BP2, CDKN2A/B
WTCCC-7UK WIDE CASE COHORTS
FTO WITH BMI
DIABETES AND GENETICS REPLICATION
AND META-ANALYSIS(DIAGRAM)
COMBINED STUDIES OF: WTCCC, DGI,
FUSION- IDENTIFIED 6 NEW LOCI:
JAFZF1, CDC123-CAMK1D, TSPAN8-LGR5,
THADA, ADAMTS9 & NOTCH2
IN EAST-ASIAN ANCESTRY:
KCNQ1, PTPRD, SRR, 13q13.1, UBE2E2
CDC4A, CDC4B
REPLICATION IN ALL POPULATIONS - A PROBLEM

13. GENES CAUSE DISEASE
COMPLEX BIOLOGICAL
SYSTEM - HUMANS
DIFFERENT TIERS OF NETWORKS OPERATE
STRUCTURAL
GENOMIC
GWA & CANDIDATE
FUNCTIONAL
GENOMIC
i) GENOMIC VARIATION & SIGNATURE
ii) TRANSCRIPTOMIC SIGNATURE / PROFILE
iii) EPIGENOMIC MARKS
iv) METABOLOMIC PROFILE
v) UNDERSTAND NETWORKING OF PATHWAYS
PHYSIOLOGICAL
VARIATIONS
INTERMEDIATE
PHENOTYPES
DISEASE

14. GENOMIC PERSPECTIVE & THE QUESTIONS POSED
REGULATION - PHENOTYPE
Nucleus
1014 cells in the body
SIGNALS
STRUCTURAL
GENOMIC
Chromatin
Mitochondrion
~3X109 + ~ 3X109
CLINICAL HETEROGENEITY
GENOTYPE-PHENOTYPE
Allelic
Heterogeneity
Same Gene
Different
(spectrum of)
mutations
PATHWAYS &
NETWORKS
FUNCTIONAL
GENOMIC
Unrelated
Phenotypes/Diseases
Locus
Heterogeneity
Different
Genes/Loci
Different mutations
Same Phenotype/
Disease

15. First Indian report pathogenic mutation E413K in
Exon 7 coding for HTM of the hHb6 gene in 13
affected members of Two Indian Monilethrix Families
Ann Genet. 2004: 47, 77-84
Ann Genet. 2004: 47, 125-7
novel Promoter, HTM and Intronic Polymorphisms in hHb6 and hHb1, the
basic keratin gene
SEM of Scalp Hair
Unaffected
Healthy hair
Affected
serration lost
Generalized-Unbeaded
Moderate SeverityFamily-2
Affected
Beaded form of hair
Localized-Beaded- confined to
Scalp; Severe Hair Defect –
Family-1

16. GENETICS AND GENOME BIOLOGY – LESSONS LEARNT IN EVOLUTION
A SUMMARY
Information available in genetics and genomics is global at cellular level – be its
Structure, expression, epigenetic regulation, pathways affected and networks
functional in cellular physiology & metabolism – yet the whole organism (systems)
level understanding is not complete.
This also relates to genotype – phenotype correlations; our genetic make-up and
susceptibilities or social/behavioural influences.
Thus it makes the system complex to analyze and we need help of concepts in physics,
chemistry, mathematics, engineering etc.
Understanding these in the evolutionary context provides a deep understanding of
who we are and how we function.

17. GENES CAUSE DISEASE
COMPLEX BIOLOGICAL
SYSTEM - HUMANS
DIFFERENT TIERS OF NETWORKS OPERATE
STRUCTURAL
GENOMIC
GWA & CANDIDATE
FUNCTIONAL
GENOMIC
THE ABOVE REQUIRES THE KNOWLEDGE BASE OF PHYSICS, CHEMISTRY,
MATHEMATICS, BIOINFORMATICS, MOLECULAR BIOLOGY etc TO
UNDERSTAND THE COMPLEX BIOLOGICAL SYSTEMS
PHYSIOLOGICAL
VARIATIONS
INTERMEDIATE
PHENOTYPES
DISEASE