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 Dr. Sanjenbam Yaiphaba Meitei Content Writer Department of Anthropology, Manipur University, Manipur Content Reviewer Prof. Barun Mukhopadhyay 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 2 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? 3 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 4 Physical/Biological Anthropology Anthropology 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. 5 Physical/Biological Anthropology Anthropology 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. 6 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