Beruflich Dokumente
Kultur Dokumente
Development Team
Prof. Anup Kumar Kapoor
Principal Investigator Department of Anthropology, University of Delhi
Pedigree analysis
Twin studies
Karypotype analysis
Adoption Studies
Biochemical methods
Epidemiological Studies
Association studies
Epigenetic studies
Summary
Learning Objective
What are the different methods for studying human genetics?
Why such methods are different from other lower organisms?
What is the concept of ‘nature nurture interaction’ in human genetics?
How can nature nurture interaction be assessed in human genetics?
What is the emerging field in human genetics, if there is any?
What are the scopes for undergoing research in human genetics?
1. Pedigree analysis
Pedigree analysis is the method to identify the mode of inheritance of any trait based on Mendelian
inheritance. It can be defined as the diagrammatical representation showing the inheritance pattern of
Mendelian traits. Certain symbols are used in the pedigree studies which are given in figure 1. The
study of the characters is started from proband (sometimes it is also known as propositus and propositia
in males and females respectively), and further traced out those who bear common characters among
his or her relatives in both preceding and following generations, as many as possible. In the chart, the
earliest generation is put at the top followed by the later generations. Different inheritance patterns
such as autosomal and sex linked: both dominant and recessive inheritance can be determined by
analyzing the pedigree. This has been used to understand the inheritance pattern of any genetic disease
or traits.
Figure 1: Symbols used in human pedigree analysis. (Source: Bodmer and Cavalli-Sforza, 1976)
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There are certain characters that are unique to each inheritance and hence it can be used to assess the
inheritance. As an example, skip of generation indicates the recessive inheritance and female being
carrier in X linked recessive inheritance.
2. Twin studies
Twin studies have been extensively used in human genetics to estimate the heritability of a particular
trait wherein relative contributions of heredity and environment may results into varied phenotypic
expression. The method analyzes genetic contribution of a particular trait as against the environmental
factors. Perhaps the first, a systematized study on twins was reported in 1924 where geneticist
Hermann Siemens compared school transcripts of identical versus fraternal twins to understand the
genetic influence on traits (Lewis, 2009. Twins can be monozygotic twin (MZ, identical) or dizygotic
twin (DZ, non identical). MZ twin results from the fusion of one sperm and one egg resulting into a
single zygote which further divides into two at the embryo stage. While DZ twin results from two
different zygotes each formed by the fusion of a sperm and an egg separately. MZ twins are of same
sex while DZ twins may be of same sex or different sex. Since MZ twin is developed from a single
zygote, it is regarded as having common genetic constitution and DZ as having different genetic
constitution like that of siblings.
Methodologically, twin studies is a longitudinal studies where the researchers compare traits of interest
in DZ twins rearing together in the same environment or in MZ twins rearing apart in different
environment or vice versa. It is based on the assumption that the differential traits developed in MZ
twins reared apart would be affect of the environmental factors. Similarly, the alike traits developed in
DZ twins reared together would be because of common environmental exposure. One of the important
measurements to find out the relative contributions of heredity and environment for quantitative
characters is Concordance scores of a trait. It is defined as the percentage of pairs in which both twins
3. Karypotype analysis
Karypotype analysis is another important method for studying human genetics. Karyotype is a
descriptive chart showing the set of chromosomes, including the diploid number, chromosome lengths,
and distinguishing morphological features of some of the chromosomes (Pasternak, 2005). In this
method, samples such as blood sample, amniotic fluid, chorionic villi or any other biological samples
containing cells are collected from an individual or patients through different techniques. Further the
sample is processed through a number of laboratory procedures such as culturing the cells (chorionic
villi cells do not need cultured as it contains enough dividing cells for analysis), cell harvesting,
separating and staining the chromosomes, scanning microscopic slides for observation etc. Cell images
are photographed and manipulated with better resolution through digital computer software. This
photographed chromosome image is kept under examination for any sort of chromosomal analysis
(National Genetics and Genomics Education Centre: http://www.geneticseducation.nhs.uk/laboratory-
process-and-testing-techniques/karyotyping). The chromosomes are captured while the cell is
undergoing cell division, particular at the metaphase stage where the chromosomes become condensed
and visible. For better analysis of the chromosome, the chromosomes are stained with certain dyes that
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Figure 3: A normal human male Karypotype: a) A metaphase array of chromosome seen under microscope, b) Arranged
chromosome in a karyotype sheet (Source: Cummings, 2010)
5. Biochemical methods
Biochemical genetics is also an important scope for understanding human genetics and its association
with certain inherited disorders. Biochemical analysis of proteins, enzymes, hormones etc. are very
much important for understanding inter or intra population variation too. Population affinities and
diversity can be estimated from the frequency of the variant of such biochemical markers. Beyond this,
biochemical analysis also reveals the fate of inherited genetic disorders. Well established scientific
techniques are very importance for the detection of such biomolecules. Quantification of such
molecules also provides another facet of biochemical analysis. Data so obtained could be compared
with the standard level, and excess and short of the same would be considered as threat to inherited
health problems, depending on the metabolic or physiological pathway that involves the analyzed
biomolecules.
6. Epidemiological Studies
Genetic epidemiological studies are again one of the important methods for studying human genetics.
As Morton has well defined that genetic epidemiology deals with etiology, distribution, and control of
disease in groups of relatives, as well as inherited causes of diseases in populations (Morton, 1982).
Different study designs have been employed to investigate the genetic epidemiological studies.
Screening of risk or mutant alleles that cause the genetic disease is one of the important aspects of
epidemiological studies. This can be applied in the detection of haemoglobinopathies or any other
genetic disorders and can assess the risk of such disorders in the population, as a whole or sex wise.
Certain specific techniques such as electrophoresis are used in the detection of mutation. Sometimes, it
is referred as descriptive epidemiology in the epidemiological science. It is obvious that collection of
biological sample, generally blood samples, is very much needed for any genetic analysis.
8. Epigenetic studies
Epigenetic analysis has brought a new trend in molecular biological research. Epigenetics deals with
inheritable changes in DNA or its associated protein without alteration DNA nucleotide sequence. It
has been considered as dynamic way by which genetic variation interacts with environmental
exposures across development to produce a phenotype (Jablonka and Lamb, 2002). It is often
associated with heritable gene expression. This new approach reassures the so called concept of nature
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In the present days especially after Human genome project, methods for studying human genetics have
become wider with the advancement of technology. Earlier it was more of study of inheritance pattern
or heritability. Such an approach has been shifted to technology based models of study wherein the
geneticists try to analyze the genes and their products. The methods may be varied but the objective is
very much defined: to understand the effect of genetic change in the phenotypic expression and also to
examine the influence of environment on genetic expression, beyond tracing the patterns of
inheritance. Such depth studies would bring a new dimension in the applied aspects too.
Summary
Genetic information is passed from one generation to the next generation in the form of
phenotypes.
Methods for studying genetics in human are quite different in human in earlier days. But it
becomes more or less same in the genomic era.
Human mating cannot be controlled as desired.
Pedigree is the diagrammatical representation showing the inheritance pattern of Mendelian traits.
Different inheritance patterns such as autosomal and sex linked: both dominant and recessive
inheritance can be determined through pedigree analysis.
Twin method analyzes genetic contribution of a particular trait as against the environmental factors
differential traits developed in MZ twins reared apart would be affect of the environmental factors.
Similarly, the alike traits developed in DZ twins reared together would be because of common
environmental exposure.
Concordant score can be defined as the percentage of pairs in which both twins express the trait
among pairs of twins in whom at least one has the trait.
Karyotype is a descriptive chart showing the set of chromosomes, including the diploid number,
chromosome lengths, and distinguishing morphological features of some of the chromosomes.
Karyotping analysis is used to detect chromosomal abnormalities – both structural and numerical.
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