Paper No.

: 01 Physical/ Biological Anthropology

Module : 31 Applied 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
Department of Anthropology, Punjab University, Chandigarh 1

Physical/Biological Anthropology
Anthropology
Applied Human Genetics
 Description of Module

Subject Name Anthropology

Paper Name 01 Physical/Biological Anthropological

Module Name/Title Applied Human Genetics

Module Id 31

Physical/Biological Anthropology
Anthropology
Applied Human Genetics
 Contents of this unit

Introduction
1. Population Variation
2. Medicine and Healthcare
a) Genetic screening
b) Genetic epidemiology
3. Personal Identification
4. Archaeogenetics
Summary
Learning Objectives

 What are the scopes of human genetics?

 What could be the role of genetic traits in population variation?
 How could the inter population variation leads to varied prognosis of complex disorders?
 What are the major areas of healthcare that human genetics can be applied for?
 What would be the effect of technological advancement in this subject matter especially in case
of forensic application?
 What could be the source of genetic information from archaeological remains?

Physical/Biological Anthropology
Anthropology
Applied Human Genetics
 Introduction

Genetics has become an important part of our daily life. As we know that genetics is about the
inheritance of genes from parental generation to next generation and also it is associated with
expression of phenotype from genotype. This basic concept of genetics can be applied to a number of
basic or applied researches as such, or it can be controlled or modified to get the desired result so. In
fact, the application of human genetics has become more broaden in the post genomic era. Applied
genetic researches are usually carried out to dig upon practical problem or to implement for the better
human society such as genetic predisposition of certain disease, solving the human evolutionary
queries, forensic application etc. In this module, some of the important application of the same is
discussed.

1. Population variation

The concept of genetics has been applied in exploring the human genetic variation, and hence depicts
the population history or evolutionary framework of biological species. Individuals in a Mendelian
population share a common gene pool that can be traced back to their ancestors. Every population has
its own genetic structure which can be defined as the distribution of alleles and genotypes in the
population. Statistical inferences play a crucial role in reconstructing the evolutionary framework. The
basic principle in this approach lies in the concept that evolution could be constructed by analyzing the
multilocus genotype on a chromosome observed in populations and their inheritance within families
(Race and Sanger, 1975).

Genetic variations in both inter and intra populations are studied through certain selected genetic
markers. Genetic markers can be either serological or biochemical traits. In the post human genome
project, genomic markers are more considered as more reliable tools for studying human genetic
variation. There are certain basic characteristics to be considered for genetic markers, such as locus
specific, polymorphic and easily genotyped. It is through these genetic variations that one’s population
structure can be determined, and at the same time inter or intra population variation can also be
evaluated through certain statistical models. Phylogenetic relationship of the population can also be
determined based on the genetic similarities and differences. Consequently, exploring human genetic
variation has become one of the important applications of human genetics and thereby trying to give an
insight on the human evolution and earliest migration.

Moreover, the knowledge of human genetic variation can also be applied in understanding the roles of
genetic variation in the development and progression of complex disorders all over the world

Physical/Biological Anthropology
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Applied Human Genetics
 population. It is assumed that the patterns of genetic variation shed light on recombination,
demography, admixture, and evolutionary selection in the human population, and thereby projecting
the underlying genetic manifestation of the diseases varied population wise. Further, population
heterogeneity may lead to spurious associations while examining the genetic role in disease
progression. It is hereby noteworthy to mention that good knowledge of population genetics or
population structure is much needed in understanding the genetic mechanism of disease progression
which may differ from population to population (Meitei et al., 2012).

2. Medicine and Healthcare

Genetic technology is now an important part of medicine, and its impact will continue to grow as
information from genomics is analyzed and applied to the diagnosis and treatment of human diseases
(Cummings, 2010). Genetics has a very important role in medical aspects thereby promoting
healthcare; hence an independent discipline has been emerged as medical genetics. With the concept of
one gene one enzyme, the importance of gene in development of Mendelian disorders or classical
single gene disorders cannot be ignored, as diseases can result from altered proteins or too little or too
much of a protein, or proteins made at the wrong place or time (Lewis, 2009). Moreover, various
complex disorders are now considered as the consequences of the interaction of gene and environment,
even the inherited ones are sensitive. Some of the application of genetics in medicine and healthcare
could be analyzed as such:

a) Genetic screening and counseling: Screening of various genetic disorders – both single gene and
complex disorders is very much essential for the promotion of common healthcare. There are a number
of inherited disorders which are lethal or sub-lethal. Screening of such lethal or sub-lethal disorders is
one of the important applications of human geneticists. It is expected that millions of people worldwide
are affected to such genetic disorders with over 10000 monogenic inherited disorders
(http://www.who.int/genomics/public/geneticdiseases/en/index2.html) and every newborn has a 3%
chance of having a genetic disorder, underscoring the need for tests that accurately diagnose heritable
diseases at all stages of life (Lewis, 2009). These monogenic disorders may be autosomal or sex linked
inheritance in either dominant or recessive patterns. Dominant inheritance will result into the
expression of phenotype or disorders in question even in presence of only one copies of mutant allele.
While for recessive traits, two copies of mutant alleles are needed to express the phenotypic trait. The
concerns of human geneticists in this regard lies in the identification of early prognosis of such lethal
or sub genetic traits especially among the newborns, and hence remedial measures can be planned
through counseling.

Physical/Biological Anthropology
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Applied Human Genetics
 Reasons to seek genetic counseling:
 Family history of abnormal chromosomes
 Elevated risk of single gene disorder
 Family history of multifactorial disorder
 Family history of familial complex disorders

Genetic counseling sessions:

 Family history
 Pedigree construction
 Information provided on specific disorders,
modes of inheritance,
 tests to identify at-risk family members
 Testing arranged, discussion of results
 Links to support groups, appropriate services
 Follow-up contact

Figure 1: Flowchart indicating steps involved in Genetic Counseling (Lewis, 2009)

Genetic counseling is the process by which the patients or relatives at risk of an inherited disorder are
advised of the consequences and nature of the disorder, the probability of developing or transmitting it,
and the options open to them in management and family planning. This complex process can be
separated into diagnostic (the actual estimation of risk) and supportive aspects (Sequeiros et al., 2012).
The person who is giving advice is the counselor and the person who is seeking is counselee.
Counselors need special attention in case of monogenic recessive disorders such as cystic fibrosis,
phenylketonuria etc. as the normal couple has the probability of giving birth to affected children in the
condition that both are carriers of the disorders. Early prognosis of such disorders is very much
essential for the babies. Besides the monogenic inherited disorders, the counselors also deals with the
complex disorders and the probable interaction of environment and gene based on the incidence of
family history of the disorder. Though the counselors talk about the causes and consequences of
genetic disorders, it is the counselee who has to take the final decision in this matter. A counselor can’t
insist the counselee to opt or decide in favour of him.

Physical/Biological Anthropology
Anthropology
Applied Human Genetics
 b) Genetic epidemiology:

Genetic Structure
Inter-Population variation
Population Genetics

Population

Genetic Epidemiology

Figure 2: Interrelationship of Population Genetics and Genetic Epidemiology through population structure and inter
population variation

Epidemiological studies is one of the another important application of genetics in the field of health
sciences. According to John Hopkins Bloomberg School of Public Health, Genetic Epidemiology is the
study of how genetic factors contribute to health and disease in families and populations, and how
genes interplay with environmental factors (http://www.jhsph.edu/departments/
epidemiology/tracks/genetic-epidemiology/). So, it can be inferred that it is the study of interaction of
genes and environments on health and disease risk in populations, which is very resemblance with
Anthropological approach of ‘Nature-Nurture’ interaction. Genetic epidemiologists attempt to identify
the many components of risk attributable to genes, environments, and interactions between these two
factors in the progression and manifestation of various disorders, especially of the complex one. In the
post human genome era, technological advancement such as implementation of genome-wide
association studies, sequencing etc., have brought a new dimension in the biomedical research with
identification of various disease susceptibility loci and interaction among each other in the phenotypic
expression of the traits under concerned. Moreover, the epigenetic approach also contributes
understanding to the role of gene and its associated factors in the varied disease expression. Genetically
no two individuals are identified, similarly one Mendelian population differ from each other in terms of
its genetic structure. Individuals in a population are believed to share a common gene pool, and hence
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 disease susceptibility loci are more or less common among the individuals of the same population.
Here, the importance of population genetic variation lies in analyzing the disease susceptibility loci in
different population and so forth different disease management programme can be taken up. The
interaction of human genetic variation in epidemiological approach is well evident through
demographic parameters (Figure 2) as the changing demographic aspects (i.e. mating patterns or
admixing) may transform the population’s gene pool, which in turn could switch on/off the clinically
important risk alleles (genes) and thereby affecting the community health with complex disorders.

Metagenomics studies are also a part of genetic epidemiological approach. The role of microbes and its
genome in understanding the overall human health can’t be ruled out. Metagenomics, the study of
genetic material recovered directly from environmental samples, has emerged as a powerful tool that
can be used to analyze microbial communities regardless of the ability of member organisms to be
cultured in the laboratory. Metagenomics could also unlock the massive uncultured microbial diversity
present in the environment to provide new molecules for therapeutic and biotechnological applications
(http://www.nature.com/nrmicro/focus/metagenomics/index.html). The application of met genomics
can be more clearly understand in the context of human nutritional studies. Nutrients are important
basic needs for human body functioning, but the problem lies that at the present the world is witnessing
dual faces of nutrition – under nutrition and over nutrition, which both are harmful to the human
health. Absorption and digestion of nutrients have biological implications. The microbes present in the
intestinal tract have a major role in the overall process. The interaction of microbes and its genomic
contents need to assess to address the human nutritional problem (Ahmed et al., 2009)

3. Forensic genetics

Personal Identification is one of the important objectives in forensic investigation on the grounds of
medico-legal context. Identification can be done through different biological traits, but genetic traits
give more precise information in this aspect. It is already established fact that no two individuals are
completely identical and this inter individual variation is more apparent when genetic analysis is made.
It may be case of paternity disputes or identification of victims or culprits involved in any forensic
related issues, could be solved through genetic identification. The application of genetics in the medio
legal context for identification of persons involved in it is referred as Forensic genetics.

In earlier, classical genetic traits have been employed for the same but in the post genomic era, DNA
profiling known as DNA fingerprinting have been used quite extensively. DNA fingerprinting also
popularly known as DNA profiling is a specialized method to analyze, compare and identify multilocus
DNA banding patterns that are specific to an individual by exposing a sample of the person's DNA to
molecular probes and various analytical techniques (The American Heritage Medical Dictionary,
2004). It was first discovered by Prof. Alec Jeffreys in the year 1984 (http://www2.le.ac.uk/study/why-
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 us/discoveries/the-invention-of-dna-fingerprinting). Biological sample can be collected from different
sources such as buccal swab, blood, saliva, semen any cellular materials and further analysis like DNA
extraction, amplification and genotyping are done. Through DNA profiling, victim identification even
in natural disasters, tragedies such as plane crashes, man-made disasters such terrorist attack or
genocide can be done. It is reported that DNA profiling been rarely used before September 11, 2001
but after the incident of World Trade Centre fall, it becomes an important tool for personal
identification even in the case of missing people (Lewis, 2009). The well publicized case of Congress
veteran leader ND Tiwari can be cited over here (http://www.rediff.com/news/report/n-d-tiwari-s-dna-
report-to-be-made-public/20120727.htm). Prior to the arrival of DNA profiling, identification can be
assessed from serological traits blood group etc. As an example, in the case of paternity dispute, the
probable father of an illegitimate child can be found out by comparing the blood groups of mother,
child and suspected father. It is based on the inheritance of blood group as O blood group parents can’t
have A or B blood group child.

4. Archaeogenetics

Human evolution itself is a mystery. There are lots of obscurities that need to be explored to have an
overall illustration of human evolution. Different stages have been constructed based on the fossil
evidence, though there are missing links which hasn’t been rectified yet. In fact, the relationship or
interaction between the extinct and extant hominids hasn’t been clearly depicted. The emergence of
population genetics in the evolutionary biology particularly in the human evolutionary studies led to
the development of new discipline ‘Archaeogenetics’ with which explains the human past through
molecular population genetics. It is defined as defines as the study of the past by use of the techniques
of molecular genetics (Renfrew and Boyle, 2000). This discipline targets to collect genetic information
from the fossil hominids, makes it compared with those of present living human population groups and
tries to decipher the genetic relationship of extinct and extant human population and overall the
probable relations with the environmental factors through statistical models. Different studies have
been come up from Europe as a number of archaeological sites are discovered in the nineteenth and
twentieth century (Trigger, 1979). The issues related with the human early demographic history are the
main concerns of the Archaeogenetics. Besides this, it also concerns with the archaic pathogens that
affects the health of extinct human through historical epidemics. The significance of Archaeogenetics
lies in the concept that it can shed light on the origins and geographical spread of prehistoric languages
and also assist archaeologists in answering questions regarding the influence of population growth in
the archaeological record (Forster and Renfrew, 2006). As an example, mt DNA analysis of modern
populations of South Asia, East Asia and Oceania reveals that there was large population expansion
before the advent of microlith technology. Through molecular clock analysis, this expansion was dated

Physical/Biological Anthropology
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 to 38-28 ka ago [kiloannus (ka): a unit of time equivalent to 1000 years] while microlith technology is
expected to started from 35–30 ka ago (Petraglia, 2009).

In summarizing the contents, the application of human genetics is increased beyond the horizon.
Biotechnological application of the same improvises the quality of human life by providing genetically
modified food crops. It also formulates the substratum for new diagnostic tests, or synthesis of
customized proteins for treating certain disease or production of vaccines in medical arena. It enhances
the concept of community health and also assist in the population specific drug designing
‘pharmcogenomics’ based on the concept that every population have unique gene pool.

Summary

 The application of human genetics in the present day world is vast.

 Gene pool of a population can be traced back to their ancestors.
 Evolution could be constructed by analyzing the multilocus genotype on a chromosome observed
in populations and their inheritance within families.
 Genetic markers can be either serological or biochemical traits.
 Genetic markers should be locus specific, polymorphic and easily genotyped.
 Patterns of genetic variation project the underlying genetic manifestation of the diseases.
 Complex disorders are now considered as the consequences of the interaction of gene and
environment.
 Screening of lethal or sub-lethal disorders is one of the important applications of human geneticists.
 Genetic counselling is the process by which the patients or relatives at risk of an inherited disorder
are advised of the consequences and nature of the disorder, the probability of developing or
transmitting it, and the options open to them in management and family planning.
 Genetic epidemiologists attempt to identify the many components of risk attributable to genes,
environments, and interactions between these two factors in the progression and manifestation of
various disorders, especially of the complex one.
 Disease susceptibility loci are more or less common among the individuals of the same population
sharing gene pool.
 Absorption and digestion of nutrients contributes to the manifestation of nutritional status of the
individual.
 The microbes present in the intestinal tract have a major role in the nutritional health.
 DNA profiling is latest technique for the identification of persons in the context of medico-legal
issues.
 Archaeogenetics reconstruct the genetic relationship of extinct and extant human population and
overall the probable relations with the environmental factors.
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Physical/Biological Anthropology
Anthropology
Applied Human Genetics