Assignment Code: MANE 001/AST/TMA/2022-23

Course Code: MANE-001

Assignment Name: Human Genetics

Year: 2022-2023

Verification Status: Verified by Professor

Attempt any five questions. Choose at least two questions from each section. 20x5

Section A

Q1) Define Human Genetics. Briefly comment on different branches of Human genetics.

Ans) A field of study called human genetics looks at how traits are passed down through the generations. The development of sophisticated laboratory and analytical methods, including biostatistics and bioinformatics tools, has allowed for a greater knowledge of the subject.

The developments in human genetics over the past fifty years have revolutionised our understanding of a variety of concepts related to health science, the treatment of disease conditions, understanding the fundamentals of biology, the causes of ethnic variations, and the evolution of living forms, including man, among others.

Branches of Human Genetics

Cytogenetics, biochemical genetics, immunogenetics, pharmacogenetics, molecular genetics, somatic cell genetics, population genetics, genetic epidemiology, genomics, and clinical genetics are a few of the subspecialties that have emerged from the field of human genetics as it has developed.

Cytogenetics: Cytogenetics is the study of chromosomes, the genetic building blocks. It has been a busy area of study that has contributed to our understanding of how chromosomes and the human genome are organised. It is a field that associates observable chromosomal aberrations with phenotypes.

Biochemical Genetics: The study of genes that regulate the activity of an enzyme that catalyses a particular biochemical process in a metabolic pathway is the focus of the field of biochemical genetics, according to its definition. A block is put in place in the biochemical pathways that are catalysed by the specific enzyme when a gene becomes faulty.

Immunogenetics: The field of immunogenetics is one that focuses on the molecular and genetic underpinnings of the immune response. In recent years, the discipline of immunogenetics has made significant contributions to our understanding of specific illnesses.

Pharmacogenetics: Pharmacogenetics, a rapidly expanding area, is the study of how medication sensitivity is passed down through human generations. The traditional illustration that can be used is the autosomal dominant characteristic of human phenylthiocarbamide or related molecule phenylthiol-urea sensitivity to taste. People who are able to taste such substances at the microscopic level are known as tasters, whereas those who are unable to taste are known as non-tasters.

Molecular Genetics: The study of genetic conditions caused by alterations in the nucleotide sequence of DNA that codes for a gene is known as molecular genetics. The detection of such circumstances requires the use of molecular biology technologies.

Somatic Cell Genetics: Somatic cell genetics is the area of genetics that deals with the fusing of somatic cells from various species in order to carry out genetic research using the hybrid cells. The development of somatic cell genetics in the 1960s was a significant advance since it eliminated the need to wait for the following generation to track the inheritance of traits from parents to offspring.

Population Genetics: A population is a collection of individuals who have interbred and their children. Population genetics examines the frequencies of various alleles in various populations as well as the factors that lead to genetic diversity among them. Penrose first concentrated on the main generalisation of population genetics in 1904, which was then succinctly stated by British mathematician Hardy and German physician Weinberg in 1908.

Genomics: The term "genomics" refers to the structural and functional analysis of the genome, which is the total amount of DNA present in an organism or cell, including the nuclear and mitochondrial genomes. The 3.2 billion nucleotides and around 20,000 genes in the human genome, as well as the gaps between them, make up the genome. The whole human genome's DNA was sequenced in April 2003 as part of the Human Genome Project.

Clinical Genetics: The field of genetics known as clinical genetics can be characterised as the study of how to treat and manage genetically based diseases and disorders. In the practise of clinical genetics, three fundamental principles genetic heterogeneity, pleiotropism, and variability should primarily be observed.

Q2) Discuss different types of chromosomal aberrations in man.

Ans) Chromosomal anomalies can be roughly categorised as structural or numerical anomalies.

Classification of Chromosomal Aberrations

Numerical Aberrations

Chromosome numbers can alter as a result of numerical aberrations. Euploidy changes and aneuploidy changes are two other categories.

1. Euploidy is the state that results in a change in the ploidy number when an organism obtains or loses one or more full sets of chromosomes.

2. When an organism loses or adds one or more chromosomes, rather than the whole set, the phenomenon is known as aneuploidy.

Euploidy situations do not exist in people because the degree of abnormalities is too great to allow for life. However, aneuploidy issues are more prevalent and show up in diseases like Down syndrome, Klinefelter syndrome, and Turner syndrome.

Different Types of Numerical Changes

Structural Aberrations

Aberrations in the structure of the chromosome are referred to as structural aberrations. These involve additions, subtractions, and reorganisations. When chromosomes separate and later re-join in different configurations from the original, structural alterations take place. An imbalanced structural alteration occurs when there is a net gain or loss of chromosomal segments. A balanced structural alteration is when there is merely a rearrangement and neither a net gain nor loss of chromosomal regions.

Q3) Write short notes on any two of the following:

a) Fluorescence in Situ Hybridization

Ans) A genetic "probe" sequence is effectively hybridised to its complementary region in the human genome. The target chromosomes are first denatured to achieve this. Of course, the probe is made up of DNA, RNA, or cDNA from the target gene. The probe, which is used to pinpoint the position of a gene on a chromosome, is essentially a segment of labelled oligonucleotide. The fundamental idea behind this approach is to select probes with higher specificity.

In earlier research, target sequences were identified using autoradiography and probes were labelled with radioactive isotopes. The sensitivity and resolution of the technology are constrained by this method of tagging and detection. The initial methodology, in instance, restricted detection to tandemly repeated sequences like satellite DNA and ribosomal genes. The insitu approach, however, had been modified by researchers by 1981 for use in mapping single copy mammalian sequences, and in 1984 a new technique had been created for higher resolution of chromosome banding patterns.

The method is still not perfect, though, as single-copy radioactive probes prevent localisation of genes within a single cell's chromosomes; instead, it calls for statistical analysis of the distributions of silver grains in 50–100 sets of metaphase chromosomes. Through the direct observation of individual chromosomes, single-copy sequence detection and high-resolution mapping are now possible thanks to two significant modifications in the methodology.

The first modification was made to the label's composition by switching radioactive tags for fluorescent ones and significantly enhancing the physical resolution of the hybridization site. FISH stands for the modified in situ procedure that makes use of fluorescent tagging. The second modification concerned the hybridization cocktail's composition. It is possible to prevent scattered repeating sequences found in nearly every genomic area longer than a few kilobases from hybridising to their targets throughout the genome by including a significant excess of unlabelled total genomic DNA.

b) ABO Blood Group System

Ans) Serum and cells are the two primary components of blood. Karl Landsteiner observed that some people's sera induced other people's red blood cells to agglutinate. The ABO blood group systems were discovered as a result of this observation. He was able to categorise people into the A, B, and O groups based on the interactions between the red blood cells and sera.

Two years later, two of his students made the rarest and fourth type AB discovery. A, B, and O groups were described by Landsteiner; the fourth type, AB, was identified in 1902 by Alfred von de-castello and Adriano sturli.

In Vienna, Austria, on June 14, 1868, Karl Landsteiner was born. He investigated immunology as it was a developing topic in 1897, and in 1901 he presented his findings on the human ABO blood type system. He developed the ABO blood typing system, which has made it possible to transfuse blood, and discovered the primary blood groups, earning him the 1930 Nobel Prize for Physiology or Medicine.

Due to the less advanced communication systems of the time, it was later discovered that Czech serologist Jan Jansky had also independently pioneered the classification of human blood into four groups, even though his name is not as well-known outside of Russia and the former USSR at the time in America, where Moss published a similar work on blood groups in 1910. The heredity of ABO blood groups was identified in 1910–1911 by Ludwik Hirszfeld and von Dungern. For identifying many alleles at a single locus as the cause of the blood group inheritance pattern in 1924, Felix Bernstein deserves credit.

Section B

Q1) What is Genetic screening and Genetic counselling? Discuss the various steps that are involved in Genetic counselling.

Ans) Genetic testing is a common diagnostic process used to identify people who are affected by genetic diseases or who are carriers of those diseases. Genetic testing is more relevant for populations than for individuals. Phenylketonuria is the condition for which genetic screening is used the most frequently in the US. A blood test known as the Guthrie test is used in all hospitals in the United States to check new-borns for PKU.

The proportion of people with genetic defects in the population is decreased and prospective parents receive clear alleviation from genetic counselling and prenatal diagnostics. These steps are unlikely to completely eradicate the harmful alleles from a population, though. This is true because heterozygotes for the majority of genetic abnormalities have recessive alleles. Therefore, even if the homozygotes for these recessive alleles were completely prevented from reproducing, they would still be present in the population through the heterozygotes, and even such harsh selection would only result in a gradual decrease in their frequency.

It has also been suggested to employ highly specialised chemical mutagens to restore the defective gene. However, the patient and embryo therapies through DNA-mediated genetic alterations may make the realisation of such a guided mutagenesis more challenging. Counselling and genetic testing may also result in issues. Among these, the instances of incorrect paternity, the issue of secrecy, and the delay in counselling are significant.

Genetic Counselling

In essence, genetic counselling is a process of communication that educates prospective parents on the nature of genetic illnesses, the possibility that they will have a child with a genetic defect, and the alternatives they have for minimising that possibility. Or it might aid them in managing the care of a child who already has genetic disabilities. The value of sophisticated knowledge in the field of applied human genetics has increased. The counsellor needs to be well-versed in the counselling process. The counsellor should ideally be a medical professional with expertise of human genetics.

A counsellor's responsibility is to provide the required genetic details as well as information on the social, economic, and psychological elements of the situation. The individuals undergoing genetic counselling are referred to as consultants. It is important to inform prospective parents about the possibility of their children contracting a genetic condition if they have the disease themselves or are suspected of having it. Such parents may be urged to deliberately abstain from having children by fostering an appropriate social environment. It is fairly simple for a trained clinician to recognise individuals with a hereditary condition.

Finding a carrier for a hereditary condition is challenging and frequently impossible. In some cases, family tree analysis can be used to determine a person's propensity to carry a genetic disease, or biochemical and molecular tests may be used to determine a person's propensity in specific cases. The steps involved in genetic counselling:

1. Following genetic screening of a problem, patients or their parents should be educated about the genetic or medical repercussions of the disease.

2. Estimating how likely it is that this hereditary issue will have an impact on the family is crucial.

3. To offer suggestions on how to stop the hereditary abnormality from happening.

Q2) What is Human Genome Project? Discuss briefly the applications of Human Genome Project.

Ans) The human genome project, which ran from 1990 to 2003, was an international research initiative with the goal of sequencing the entirety of human DNA and pinpointing the locations of all known genes. The National Institutes of Health and the U.S. Department of Energy coordinated this initiative. The initiative was started with the intention of creating new techniques for identifying, managing, and eventually curing the myriad of ailments that impact humans.

After this experiment was finished, a vast amount of genetic data was made available. Every adult has a right to be aware of their genetic makeup and how it may affect the health of future generations. Regarding issues like access to genetic information, diagnostic services, privacy and confidentiality, disclosure to family members, freedom of reproductive choice, misuse of genetic information, stigmatization/discrimination of individuals based on their genetic make-up, etc., HGP has expressed some concerns.

The Human Genome Project attempts to map the whole human genome, define its intricate architecture, and pinpoint the order of chemical base pairs that make up human DNA. DNA nucleotide sequence variations are the cause of variations in genetic make-up. The mapping of the human genome has always been a priority for scientists. DNA fragments may now be isolated, cloned, and have their nucleotide sequences determined thanks to improvements in genetic engineering techniques.

In order to identify and map every gene in the human genome from both a physical and functional perspective, as well as to determine the sequence of nucleotide base pairs that make up human DNA, the Human Genome Project was an international scientific research endeavour. The Human Genome Project had numerous objectives. Some of the significant objectives were listed below:

1. To catalogue all 20,000–25,000 genes that make up human DNA.

2. To ascertain the 3 billion base pair sequences that constitute up human DNA.

3. To enter this data into the database.

4. To create makeshift instruments for data analysis.

5. To transfer relevant technologies to other businesses or areas.

6. To handle the project's potential ethical, legal, and social challenges.

Applications of Human Genome Project

1. The possibility of creating gene-based remedies for both inherited and acquired disorders is also made possible by the discovery of new genes.

2. Its comprehensive genetic, physical, and sequence maps will be essential in understanding the biological underpinnings of complex disorders like diabetes, heart disease, cancer, and psychiatric illnesses like alcoholism that are brought on by the interaction of many genetic and environmental factors.

3. It aids in the discovery of mutations connected to various cancer types.

4. Additionally, it advances forensic science studies.

5. Other industries that have benefited from the utilisation of human genome projects include agriculture, the environment, and biotechnology.

Aiming to discover, map, and sequence every gene in the human genome from both a physical and functional perspective, the Human Genome Project was an international scientific research endeavour. Each person has a distinct "genome," so to map the "human genome," a small sample of people must be sequenced, followed by their sequences being put together to create a complete sequence for each chromosome.