Population genetics and

Population genetics and Genetic counseling: 

Population genetics and Genetic counseling Dr Naresh T Chauhan

Historical aspects: 

Historical aspects Homosapiens first appeared on this planet approximately 50,000 years ago Gregor John Mendel 1865 Johnson coined the term “gene” 1962 -Watson, crick and Maurice DNA structure “Human Genome Project” started in 1991 Gene therapy 2

Cell structure: 

Cell structure 3

Cellular basis of inheritance: 

Cellular basis of inheritance genes are made up of DNA DNA sequences make up genes which code for different proteins necessary for life The process whereby genetic information is transmitted from DNA to RNA is called “ transcription ” The transmission of the genetic information from mRNA to protein is called “ translation ” 4

Chromosomes, genes and DNA: 

Chromosomes, genes and DNA 5

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Structure of Gene: 

Structure of Gene 7

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CHROMOSOME NUMBER: 

CHROMOSOME NUMBER NUMBER OF SETS OF CHROMOSOMES – PLOIDY (n) n – Monoploidy / Haploidy 2n – Diploidy 3n – Triploidy 4n – Tetraploidy 5n – Pentaploidy 6n – Hexaploidy 7n - Heptaploidy 10

Mutations: 

Mutations A mutation is defined as an alteration or change in the genetic material due to exposure to mutagenic agents Spontaneously through errors in DNA replication and repair Occurrence of mutations in DNA, if left unrepaired, would have serious consequences both for the individual and subsequent generations 11

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Genetic disorders arise from either structural or numerical change in the chromosome(s) or gene(s) of autosomes or sex chromosomes 12

Structural Chromosomal abnormalities : 

Structural Chromosomal abnormalities Deletion Inversion Translocation Duplication Transverse centromeric division Numerical Chromosomal abnormalities Aneuploidy and Polyploidy 13

Chromosomal deletion: 

Chromosomal deletion 14

Chromosomal inversion: 

Chromosomal inversion 15

Balanced translocation : 

Balanced translocation 16

Unbalanced translocation: 

U nbalanced translocation 17

Chromosomal duplication: 

Chromosomal duplication 18

Aneuploid/ polyploid cells arise due to following events: 

Aneuploid/ polyploid cells arise due to following events Nondisjunction Anaphase lag Multiple gametic fertilization 19

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Nondisjunction: 

Nondisjunction 21

Nondisjunction, Anaphase lag, Multiple gametic fertilization: 

Nondisjunction, Anaphase lag, Multiple gametic fertilization 22

Burden of Genetic Disease: 

Burden of Genetic Disease “Gene pool”, customs regarding marriage (breeding patterns) and migrations diseases caused due to mutations of ancient origin are likely to be distributed throughout the population diseases due to mutation which have arisen more recently may be restricted or even unique to individual ethnic groups, subcastes, tribes or clans large population, high birth rate and of consanguineous marriage 23

Incidence and Prevalence of Genetic disease: 

Incidence and Prevalence of Genetic disease every year 4,95,000 infants with congenital malformations 3,90,000 with G-6 PD deficiency 21,400 with Downs Syndrome 9,000 with thalassaemia - estimated 20 million carriers(1-15%) 5,200 with sickle cell disease - tribal communities (50%) 9,760 with amino acid disorders 24

Categories of Genetic Disease: 

Categories of Genetic Disease Chromosomal Disorders Trisomy (50 percent) Monosomy X (20 percent) Triploidy (15 percent) Tetraploidy (5 percent) Others (10 percent) Single Gene or Mendelian Disorders Sex Linked Inheritance Mitochondrial Genetic Disorders Multifactorial Disorders Acquired Somatic Genetic Disease 25

Public Health Issues in Genetic Diseases: 

Public Health Issues in Genetic Diseases Epidemiological studies have helped us understand how genetic diseases are distributed in a population to identify genetically susceptible individuals early detection and even management gene therapy 26

Primary Prevention: 

Primary Prevention Eugenics : It is science of improvement of genetic endowment through breeding “ Positive Eugenics ” seeks to improve the genetic endowment in the population of “ favourable traits ” by encouraging persons with these traits to intermarry “ Negative Eugenics ” in which people suffering from serious disorders which are genetic in origin are debarred from producing children as new mutations continue to occur negative eugenics can not be an effective public health tool 27

Genetic Counseling: 

Genetic Counseling Definition? Consultand : The individual ( not necessarily affected ) who presents for genetic counseling and through whom a family with an inherited disorder comes to medical attention Genetic counseling is non directive, with no attempt to lead the consultand in any particular direction Commonly, people seek counseling after the occurrence of a hereditary disorder in the family Rarely, individuals / couples may seek pre-marital advice 28

Genetic Counseling…….: 

Genetic Counseling……. During genetic counseling, the counselor tries to provide the consultand with information which enables him/her to understand : The medical diagnosis and its implications in terms of prognosis and possible treatment Mode of inheritance of the disorder and the risk of developing and / or transmitting it Choices or options available for dealing with the risks “retrospective” , “prospective” counseling contraception, pregnancy termination or even adoption of a child 29

Steps in Genetic Counseling: 

Steps in Genetic Counseling Establishment of diagnosis Calculating and presenting the risk Discussing the options Communication and support 30

Establishment of diagnosis: 

Establishment of diagnosis most crucial step history taking, detailed clinical examination and appropriate investigations The family history may need to be obtained by a properly trained genetics nurse or counselor Chromosomal and molecular studies will also be needed to establish the inheritability and genetic basis of the disease “genetic heterogenosity” congenital cataract (AD, AR, XR), ichthyosis (AD, AR,XR), retinitis pigmentosa (AD, AR, XR) and polycystic kidney disease(AD, AR) 31

Calculating and presenting the risk: 

Calculating and presenting the risk Based on the genetic diagnosis and calculation of risk based on well established norms The risk needs to be qualified by aspects like long term burden rather than its precise numerical value 32

Continue…..: 

Continue….. Whether a disease can be successfully treated, associated with pain and suffering and whether pre-natal advice is available can be relevant to the decision making process As an arbitrary guide, risk of 1 in 10 or greater can be regarded as high while 1 in 20 or less can be regarded as low 33

Discussing the options: 

Discussing the options natural follow up after making the diagnosis and presenting the “risks” All the choices should be provided with no attempt made to guide the consultand to select one of them The issues need to be broached with care and sensitivity 34

Communication and support: 

Communication and support Provided by most genetic counseling clinics The setting of the counseling must be agreeable, private and quiet with ample time for discussion and questions Technical terms must be avoided No attempt must be made to hide facts and questions answered honestly and openly A letter summarizing the topics discussed is then sent to the Consultand 35

Other Health Promotional Measures: 

Other Health Promotional Measures Restrict pregnancies arising from late marriages or in women past 35 years Consanguineous marriages Hearing loss, mental retardation, alkaptonuria are common among offsprings of consanguineous marriages 36

Specific Protection: 

Specific Protection Radiation- X-Ray and other ionizing radiations Chemicals -mustard gas, benzene, formaldehyde Drugs- avoided in pregnancy Genetic effects are known to be cumulative and protection is routinely provided to all those who are likely to be occupationally exposed to radiation 37

Early Diagnosis: 

Early Diagnosis Population genetic screening programs to enable individuals to be better informed about genetic risks and reproductive options prevention of morbidity due to genetic diseases and alleviation of the suffering 38

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