Assignment Code: BANC-111/ASST/TMA/January 2022

Course Code: BANC-111

Assignment Name: Human Population Genetics

Year: 2022

Verification Status: Verified by Professor

Total Marks: 100

Read the instructions carefully and answer accordingly. There are three Sections in the Assignment. Answer all questions from all the sections.

Assignment I

Answer the following in about 500 words each. 20x2= 40

a. Briefly discuss various evolutionary forces that shape the genetic variation.

Ans) The various evolutionary forces that shape the genetic variation are:

Mutation

Mutation is a change in the genetic material that is handed down from one cell to the next. Mutations are alterations in the genetic code that occur at random. Because mutations fuel population diversity and hence permit evolutionary change, they are one of the fundamental forces of evolution. Evolutionary effects, on the other hand, only come from germline modifications, not from changes in somatic tissues. Physical changes to the genetic material generate mutations, and because DNA is a long sequence of base pairs structured into physically unlinked chromosomes, it can alter in a variety of ways.

Natural Selection

Natural selection is the adaptation and modification of populations of living organisms. Individuals in a population are naturally varied, which means they differ in certain respects. Because of this variety, some people have features that are better suited to their surroundings than others. Natural selection is completely reliant on the surrounding environment. Adaptive characteristics (traits that provide you an advantage) increase your chances of surviving and reproducing. These people then pass on their adaptive features to their children. These beneficial features become more prevalent in the population over time. Beneficial qualities are passed down across the generations as a result of natural selection.

Gene Flow

The movement of alleles from one group to another through migration is known as gene flow. Emigration (when new organisms join a population, bringing new alleles or changing frequencies) or immigration (when new organisms join a population, bringing new alleles or changing frequencies) can both cause changes in the population's relative allele frequencies (when members of a population leave it, taking with them their genes). Admixture is introduced as a result of migration. We can think of America as a place where both coloured Africans and white Europeans have migrated. There was mixing between these populations, resulting in a mixed population. If you have a child and relocate to a different population, your genes will have shifted as well. As a result, one of the variables that causes changes in allele frequencies in a population is migration.

Genetic Drift

Random changes in allele frequencies in a population caused by chance events are known as genetic drift. To be more precise, genetic drift occurs as a result of "sampling error" in picking alleles for the future generation from the present generation's gene pool. Its effects are more pronounced in small groups.

Inbreeding

Random mating is uncommon in the mating patterns of organisms in a population. Mating between similar individuals occurs more frequently than chance would predict in positive assortative mating, also known as consanguineous mating or inbreeding. As a result, compared to random mating, the frequency of homozygotes increases.

Recombination

During meiosis, recombination is the exchange of genetic information between homologous chromosomes. Recombination creates new combinations of alleles, increasing genetic diversity in this way. Recombination, on the other hand, can disrupt beneficial allele combinations, leading to a loss of fitness known as "outbreeding depression."

b. What is Genetic polymorphism? Briefly discuss various genetic markers that exhibit polymorphism.

Ans) Genetic polymorphism occurs when two or more discontinuous forms or phases of a species coexist in the same habitat in such large numbers that the rarest of them cannot be perpetuated by recurrent mutations. In layman's terms, genetic polymorphism is the presence in the same population of two or more alleles at the same locus, where the frequency of the rarer allele is always more than one percent and the rarer allele is maintained in the population, not just by recurrent mutations.

The various genetic markers that exhibit polymorphism are as follows:

Serological Markers

Serological signals are best illustrated by blood types. ABO and Rh blood types are two of the most essential serological markers in blood transfusion and organ donation. Landsteiner's discovery of the ABO blood group system is an example of tri-allelic inheritance. Mendelian inheritance is followed by these markers. The ABO blood group's genetic system is found on chromosome 9 and consists of three primary alleles: A, B, and O. In this case, the A and B alleles are co-dominant, while the O allele is recessive. The phenotypes A, B, AB, and O are found in all populations, but their proportions differ depending on where they are found. The ABO blood type is one of the most researched genetic polymorphism systems in the Indian subcontinent, with the B allele frequency being the greatest in most ethnicities.

Biochemical Markers

Individuals in a community are known to differ based on biochemical indicators such as human red cell enzymes such as adenylate kinase, phosphoglucomutase, G6PD, and serum proteins such as haptoglobin, transferrin, immunoglobulins, and others, as well as haemoglobins and thalassaemia. One of the most well-studied polymorphisms is glucose 6 phosphate insufficiency. The G6PD gene is found on the X chromosomes long arm (Xq28) region chromosomal. It's an 18-kilobyte gene with roughly 13 exons that's transcribed into a 2.269-kilobyte messenger RNA with a 1.545-kilobyte coding region. Beutler and Mitchell, 1968 developed the simplest fluorescent spot test to identify G6PD deficiency in male individuals. The approach is based on the fluorescence of NADPH, which is produced by a small amount of G6PD enzyme.

Molecular Markers

A DNA polymorphism is a sequence difference that occurs in at least 1-2 percent of the population when compared to a reference standard. Genetic polymorphism can appear in DNA sequences in a variety of ways. There are various forms of genetic polymorphisms, based on the number of nucleotides involved in the polymorphism as well as the rationale for the changes.

DNA polymorphism can be studied in the following forms:

1. Single Nucleotide Polymorphism (SNP)

2. Restriction Fragment Length Polymorphisms (RFLP)

3. Variable Number of Tandem Repeats (VNTR)

4. Insertion Deletion Polymorphisms

5. Lineage Markers

i) Mitochondrial Markers

ii) Y Chromosomal Markers

Assignment II

Answer any two of the following questions in about 250 words each. 10x2=20

a. What are complex diseases? Briefly discuss the role of environmental factors affecting complex diseases.

Ans) Disorders that are ultimately determined by a mix of hereditary and environmental factors are referred to as complex or multifactorial diseases. In other words, 'Complex Disease' is a complex trait that is polygenic in origin, meaning it is controlled at the cellular level by more than one gene or many genes. Such a condition or trait is the result of a complex interaction between hereditary characteristics and environmental variables, referred to as "nature and nurture."

The role of environmental factors affecting complex diseases is:

Nutrition

Nutrition, or the food we eat, has a direct impact on almost all complex diseases. Our eating patterns have altered dramatically since our prehistoric predecessors. Our predecessors, for example, ate naturally occurring plant foods and wild animals, whereas we derive the majority of our calories from cereals, domesticated cattle, dairy products, and processed sweets. Cereal grains, dairy products, separated oils, and professionally prepared meals were nearly never consumed. In fact, our forefathers ate twice as much animal protein as today's western populations. One of the most important reasons for complicated diseases is a drastic shift in nutrition intake from fruits and vegetables to dairy and cholesterol-rich diets.

Physical Inactivity

Physical activity has a significant impact on muscular strength and skeletal robusticity, both of which our forefathers possessed. Lack of physical activity leads to the formation of large fatty tissues in our bodies, increasing our risk of diabetes, atherosclerosis, and other complex disorders.

Psycho-social Factor

Human behaviour genes are ancient, and they most likely evolved in the same way as other physical characteristics. The social circumstances of contemporary societies, such our current sedentary lifestyle and nutrition, are fresh and quite different from those of our forefathers. These psychological factors increase the likelihood of acquiring a variety of complex diseases in the long run.

b. Briefly describe different types of Haemoglobin (Hb) variants

Ans) The different types of Haemoglobin (Hb) variants are:

HbS (Sickle Cell Haemoglobin)

This condition is also known as sickle cell disease. It is a monogenic disorder that is inherited in an autosomal recessive manner. Vaso-occlusion causes damage to the kidneys, retina, spleen, and liver in HbSS patients. Hypoxia, hypertonic solutions, fever, illness, temperature changes, and excessive exertion can all trigger symptoms.

HbE (Haemoglobin E)

This is a widespread Hb variation in Southeast Asia, with a prevalence of about 50% in some Thai ethnic groups. This is caused by a single point mutation in the beta globin gene that swaps glutamic acid with lysine at codon 26. As a result, aberrant RNA processing takes place, resulting in irregular RBC. Jaundice, enlargement of the liver and spleen, and growth retardation are all symptoms of the HbE variation. The severity of symptoms is determined by the presence of -thalassemia in the family.

HbC (Haemoglobin C)

The amino acid lysine was substituted for glutamic acid at position 6 of the globin, resulting in this Hb variation. Homozygotes have mild haemolytic anaemia, but heterozygotes are asymptomatic. They produce chronic haemolytic anaemia when coinherited with HbS, and moderate haemolytic anaemia with splenomegaly when coinherited with thalassemia. It has been demonstrated that in a homozygous form, this Hb variation gives protection against Plasmodium falciparum, while in a heterozygous state, it provides intermediate protection.

HbD (Haemoglobin D)

Haemoglobin D-Punjab or haemoglobin D-Los Angeles are two names for this Hb variation. It was created when a point mutation in the beta globin gene caused glutamine to be replaced by glutamic acid in the first base of codon 121. Homozygous individuals experience mild to moderate haemolytic anaemia, while heterozygous individuals experience no clinically relevant symptoms. It can also be passed down in families with thalassemia or HbS. HbD with -thalassemia co-inheritance results in mild microcytic and hypochromic anaemia.

c. Briefly comment on the super family Hominoidea.

Ans) Hominoidea is the superfamily that includes both extinct and living apes and humans. Pongidae and Hominidae are the two families that make up the superfamily Hominoidea. Ponginae and Hylobatinae are two subfamilies of the Pongidae family. Hylobates is the only genus in the Hylobatinae family, containing three species (H. lar, H. moloch and H. Syndactylus or Gibbons and Siamangs). Furthermore, the Hominidae family includes all living and extinct humans.

The Pongidae

1. Pongo (Orangutan), Pan (Chimpanzee), and Gorilla are members of the Ponginae family of gigantic apes. The name "ape" refers to all members of the Ponginae family, whereas "big apes" refers to the Chimpanzee and Gorilla. Pongids are the closest relatives of humans.

2. Pongo (Orangutan): Of all the hominoid primates, they are the most mysterious. They are typically solitary apes as compared to other apes. Orangutans have a huge body and are sexually dimorphic to an extreme.

3. Pan (Chimpanzees and Bonobos): Chimpanzees and Bonobos are similar to gorillas in appearance. Chimpanzees and bonobos have a body proportion that is approximately identical to that of a man.

4. Gorillas are the largest and stoutest of all extant primates, but they are also the shyest and gentlest.

5. The Gibbons, sometimes known as lesser apes, are part of the Hylobatinae family. Lesser apes are referred to as such since they are smaller than bonobos, chimps, gorillas, and orangutans. They're tree-dwelling creatures.

The Hominidae

It is currently divided into a single genus, Homo, and a single species, Sapiens. The cranium of Homo sapiens is quite big. At the base of the skull, the foramen magnum is placed more anteriorly. As a result, the head is perfectly balanced. Under the anterior cerebral fossa, the orbits are placed. Jaw projection has been reduced significantly. Orthognathism is a condition that affects the face. The alveolar arches are smaller and more fragile. The nose is extended, with a well-developed nasal bridge, and the chin is well-developed. Canines are small and bluntly pointed in humans. They don't put forth a lot of energy. Humans are most similar to gibbons among the apes in terms of low canine sexual dimorphism.

Answer the following questions in about 50 words each. 2x5=10

a. Hardy-Weinberg Law

Ans) "In the absence of any evolutionary impacts from one generation to the next, the genotype and allele frequencies in a vast, random-mating population stay constant." Natural selection, genetic drift, mutation, sexual selection, gene flow, genetic hitchhiking, founder effect, meiotic drive, population bottleneck, inbreeding, and assortative mating are all factors to consider."

b. Diabetes

Ans) Diabetes is a condition in which your blood glucose, often known as blood sugar, is abnormally high. Your main source of energy is blood glucose, which comes from the food you eat. Insulin, a hormone produced by the pancreas, aids glucose absorption into cells for use as energy.

c. Gene Flow

Ans) Gene flow, also known as gene migration, is the transfer of genetic material from one population of a species to another, altering the composition of the recipient population's gene pool. The movement of alleles from one group to another through migration is known as gene flow. Migration, either by immigration or emigration, can affect changes in the population's relative allele frequencies. Admixture is introduced as a result of migration.

d. Positive Assortative Mating

Ans) When people choose to mate with people who are similar to themselves (for example, when a tall person mates with another tall person), this is known as positive assortative mating, or homogamy. Negative assortative mating occurs when people avoid mating with people who are similar to them.

e. G6PD deficiency

Ans) G6PD insufficiency is a hereditary condition that primarily affects men. It occurs when the body's supply of an enzyme called glucose-6-phosphate dehydrogenase is insufficient (G6PD). G6PD aids the function of red blood cells. It also protects them from potentially harmful elements in the blood.

Assignment III

Answer the following questions in about 250 words 10x3=30

a. Briefly describe the procedure for phenotyping of ABO and RH blood groups with suitable diagrams.

Ans) On a porcelain tile, glass slide, microcentrifuge tube, or microplate, phenotyping or blood type determination is performed. Antisera that are commercially accessible are used to phenotype blood types.

The procedure for phenotyping of ABO and RH blood groups is as follows:

1. Incubate the Rh-(negative) microcentrifuge tube (1mL) for 30 minutes at 37oC in a water bath, following the process outlined in 1.3.3.

2. In a minicentrifuge, centrifuge the microcentrifuge tube for 1 minute at 1000 rpm.

3. Consider Rh+ if RBC agglutination is observed (positive). If there is no agglutination, move on to the next stage.

4. Using a 1mL micropipette, add 800l of 0.9 percent saline to Rh-containing microcentrifuge tubes, centrifuge at 1000rpm in a minicentrifuge, and remove the supernatant (liquid). This procedure should be repeated three times.

5. Using a 1mL pipette, add 200 l of anti-human globulin to the microcentrifuge tube.

6. Gently touch the microcentrifuge tube with your finger to gently shake it and look for RBC agglutination under a light or microscope.

7. If RBC agglutination is observed in a microcentrifuge tube, the existence of weak D (Du)+ is confirmed, and if it is not, Rh- is determined (negative).

Water Bath

Microscope

b. Describe the procedure to detect colour blindness using Ishihara test plates.

Ans) The Ishihara test is a frequently used test for detecting colour vision deficiency/colour blindness. Shinobu Ishihara of Japan created this test, which has been in use since 1929. This test can be used to screen for red-green colour blindness and distinguish between protan and duetan abnormalities in children as young as five years old. The commonly utilised test is carried out with the aid of 38 plates or charts.

The procedure to detect colour blindness using Ishihara test plates is as follows:

1. In a well-lit room, the plates are held at a distance of about 75cm and at right angles to the participant's line of vision.

2. Each reading of the numerals in plates Nos. 1-25 should take no more than three seconds.

3. To measure the participant's visual defect, the numerals identified by the subject are matched with the standard table.

4. When a participant can read 17 or more plates, he or she is said to have normal colour vision. If the individual can only read 13 plates or less, he or she is diagnosed with red-green colour vision insufficiency.

5. Abnormal participants include those who can read numerals 5, 2, 45, and 73 in plate numbers 18, 19, 20, and 21, as well as those who can read numerals more easily than those on plates 14, 10, 13, and 17.

6. The plates 22, 23, 24, and 25 are used to distinguish between protan and deutan forms of colour vision.

7. If a participant cannot read red numerals, he or she is labelled protan, and if they cannot read red-purple numerals, they are labelled deutan.

c. What is PTC taste sensitivity? Briefly comment on the technique to detect tasting ability of a person using serial dilution method.

Ans) Phenylthiocarbamide is a crystalline chemical molecule that is also known as Phenylthiourea, N-Phenylthiourea, 1-Phenylthiourea, or 1-Phenyl-2-Thiourea. One of the hydrogen atoms in this chemical is replaced with a phenyl group, making it a thiourea. PTC has the chemical formula C7H8N2S and a molecular weight of 152.22. PTC taste sensitivity is the most extensively utilised genetic marker for investigating human diversity after blood types. Some people can't stand the taste, while others find it quite bitter. Those who are sensitive to PTC's taste are referred to as 'tasters,' while those who are not are referred to as 'non tasters.'

The following is the procedure for detecting a person's capacity to taste using the serial dilution method:

Suprathreshold or threshold approaches can be used to assess PTC taste sensitivity. The threshold approach identifies taste sensitivity at low doses, whereas the suprathreshold method assesses test intensity at greater concentrations using rating scales. The need of several samples over a range of doses and sensitivity variations in assessing taste sensitivity are two drawbacks of the suprathreshold approach. The Harris and Kalmus threshold approach is the most extensively utilised protocol for separating PTC tasters from non-tasters.

The first step in this procedure is to make a stock solution by dissolving 1.3 g of phenylthiocarbamide in 1 litre of boiling tap water, which is referred to as solution No. 1. The following serial dilutions are made from the stock solution, as stated in table 4.1. Take 50 ml of the stock solution (solution No. 1) and mix it thoroughly with 50 ml of hot tap water. Label it as solution No. 2. To prepare solution No.3, take 50 mL of this solution and mix it with 50 mL of heated tap water. Similarly, from solution No. 1 to 14, a series of serially diluted solutions is created.