Paper No.

: 01 Physical/ Biological Anthropology

Module : 23 Methods of Studying Human Genetics

Development Team
Prof. Anup Kumar Kapoor
Principal Investigator Department of Anthropology, University of Delhi

Prof. Subho Roy

Paper Coordinator Department of Anthropology ,University of Calcutta

Content Writer Dr. Sanjenbam Yaiphaba Meitei

Department of Anthropology, Manipur University, Manipur

Prof. Barun Mukhopadhyay

Content Reviewer
Indian Statistical Institute, Kolkata
Prof. K.D.Sharma
1 Department of Anthropology, Punjab University, Chandigarh

Physical /Biological Anthropology

Anthropology
Methods of Studying Human Genetics
 Description of Module

Subject Name Anthropology

Paper Name 01 Physical/ Biological Anthropology

Module Name/Title Methods of Studying Human Genetics

Module Id 23

Physical /Biological Anthropology

Anthropology
Methods of Studying Human Genetics
 Contents of this unit
 Introduction

 Pedigree analysis

 Twin studies

 Karypotype analysis

 Adoption Studies

 Biochemical methods

 Epidemiological Studies

 Association studies

 Population genetics 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?

Physical /Biological Anthropology

Anthropology
Methods of Studying Human Genetics
 Introduction
As we already know that human genetics concerns the scientific study of inherited human variation.
Genetic information is passed on from parental generation to the younger generation and it is expressed
in the form of phenotypic characteristics. Though genetic is basic approach to understand the
inheritable variation in all organisms, the methods of study the same in human is quite different and
unique from those of other organisms. It is due to the fact that human’s life cycle is inconveniently
long and family sizes are too small to undergo such studies. Moreover, it is difficult or illegal to
procure desired matings as can be done in lower organisms. In this module, some of the important
methods for studying human genetics will be discussed.

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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 I

II

III

IV

Figure 2: A hypothetical pedigree indicating autosomal recessive inheritance

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

Physical /Biological Anthropology

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Methods of Studying Human Genetics
 express the trait among pairs of twins in whom at least one has the trait (Lewis, 2009) Twins sharing a
common phenotype are said to be concordant and as well twins sharing different phenotype are said
discordant. Twin studies have been considered as important method to assess nature (genetic) and
nurture (environment) approach. Twins both MZ and DZ reared apart shows that the influence of
genetic and environmental factors in phenotypic expression. Concordant traits developed in twins
reared apart indicate the role of genetic factors.

Table 1: Concordance values in MZ and DZ twins (Source: Cummings, 2010)

Concordance Values
Trait MZ Twins DZ Twins
Blood Types 100 66
Eye Color 99 28
Mental Retardation 97 37
Hair Color 89 22
Down Syndrome 89 7
Handedness (Left or Right) 79 77
Epilepsy 72 15
Diabetes 65 18
Tuberculosis 56 22
Cleft Lip 42 5

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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 show patterns of light and dark bands. Such technique is commonly known as banding technique and G
banding, which uses a dye called Giemsa’s reagent, being the common one. This method has been
employed to analyze the chromosomal abnormalities – both structural and numerical. Numerical
abnormalities may be trisomy and any other excess or less of diploid chromosomes, while structural
abnormalities include deletion and insertion of segments, translocation etc. Such detection of
chromosomal abnormalities would be helpful in understanding the prognosis of genetic disorders.

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)

Physical /Biological Anthropology

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Methods of Studying Human Genetics
 4. Adoption Studies
Adoption Studies are also other methods to investigate the nature nurture approach. It is well
established fact that the adopted children do not share the genetic constituents with the adoptive
parents. Comparison of adopted children with biological and non biological parents can provide an
understanding on the heritability of the traits. Concordant characters between the adopted children and
the non biological parents would be assessed as the influence of environmental factors. This method
has been extensively used in analyzing the heritability of behavioral traits. Adoption studies have
shown that the children born out of schizophrenic parents and adopted by non schizophrenic parents
have higher chance of developing the disorder than the children out of normal biological parents and
adopted by the same (Pasternak, 2005). This method has some limitations too as such studies require
access to good adoption records and stable populations over generations, so there are a limited number
of situations in which they can be used (Stanford et al., 2013).

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.

Physical /Biological Anthropology

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Methods of Studying Human Genetics
 Association studies are also important facet of human genetic studies. Such studies are carried out to
examine the possible associations of certain mutations or any other genetic factors in the development
of genetic disorders, generally in such polygenic inherited traits or disorders. The role of these genetic
factors in the disease progression and manifestation may differ from one population to another.
Association studies can be family based or population based association studies. Case control or case
only studies are some of the models of association studies. In case control studies, the affected
individuals or those at risk are considered as case and those who don’t possess the characters of being
case are included as controls. Association of risk mutant alleles or other genetic factors are assessed
through statistical approach. In population based association studies, both case and controls are
collected from the age sex matched individuals from the same population as different populations have
varied gene pools. But in the case of family based association studies, controls are the family members
who are not affected by the trait under consideration.

7. Population genetics Studies

Population genetics is an important branch of genetics dealing with describing the genetic structure of
a Mendelian population. It has been considered as a focal point for evolutionary biology where in
change in the allele and genotypic frequencies would determine the evolutionary fate of any
population. Moreover, the genetic relationship of inter and intra population in the form of genetic
differentiation and similarities can also be accessed through statistical methods. Statistics plays a very
important role in analyzing and interpreting inter or intra genetic relationship of the populations. Such
studies are carried out through certain genetic markers. Genetic markers can be either serological,
biochemical or genomic markers. The allelic and genotypic frequencies of these markers are calculated
based on the observed frequencies of the traits or phenotypes, which have been collected from the
population through sampling approach. Analysis of genomic markers need sophisticated techniques
such as DNA extraction, PCR amplification, genotyping etc. Genotyping is requisite technique even in
serological and biochemical markers to identify the variant of the traits. Certain statistical analyses are
done from the allele frequencies calculated and the results describe the genetic structure of the
population. Secondary information such as population and mythological histories etc, provide an
important validation in the findings of the genetic results. Population genetic studies have become a
basic substratum for population stratification which could be used in epidemiological studies.

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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 nurture interaction. Environment may provide change in the expression of genetic trait without
modification of genetic elements of the individual. There are different methods to undertake epigenetic
analysis such as histone modification and DNA methylation. It is well established that abnormal
patterns of DNA methylation are associated with various complex disorders. Lower-than-normal levels
of methylation (demethylation or hypopmethylation) are commonly observed in some types of cancer
as removal of methyl groups can activate genes involved with cell growth and can increase genomic
instability (Cummings, 2010). Depth knowledge in the subject matter would be required to design such
studies. It is true that the approach of epigenetics in Anthropological investigation is less, but it needs
to be given emphasis in the present scenario.

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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Methods of Studying Human Genetics
  Concordant characters between the adopted children and the non biological parents would be
assessed as the influence of environmental factors.
 Biochemical analysis of proteins, enzymes, hormones etc. are very much important for
understanding inter or intra population variation too.
 Biochemical analysis of enzymes, proteins etc. also reveal the fate of inherited genetic disorders.
 Screening of risk or mutant alleles that cause the genetic disease is one of the important aspects of
epidemiological studies.
 Association studies are carried out to examine the possible associations of certain mutations or any
other genetic factors in the development of genetic disorders, generally in such polygenic inherited
traits or disorders.
 Association studies can be family based or population based association studies.
 The genetic relationship of inter and intra population in the form of genetic differentiation and
similarities can be accessed through statistical methods in population genetics methods.
 Genetic markers can be either serological, biochemical or genomic markers.
 Secondary information such as population and mythological histories etc, provide an important
validation in the findings of the genetic relationship of inter population.
 Epigenetics deals with inheritable changes in DNA or its associated protein without alteration
DNA nucleotide sequence.
 Environment may provide change in the expression of genetic trait without modification of genetic
elements of the individual.

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Physical /Biological Anthropology

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Methods of Studying Human Genetics