Introduction to Genetic Dr Rosline Hassan Department of Haematology School of Medical Sciences University Sains Malaysia

Table of contents Chromosome DNA Protein synthesis Mutation Genetic disorder Relationship between genes and cancer Genetic testing Technical concern

Chromosome All living organisms consist of cells. In each cell there is chromosomes. Chromosomes are strings of DNA Chromosome consists of genes, blocks of DNA. Each gene encodes a particular protein.

Chromosome Each gene has its own position in the chromosome. This position is called locus. Complete set of genetic material (all chromosomes) is called genome. Particular set of genes in genome is called genotype. The genotype is with later development after birth base for the organism's phenotype, its physical and mental characteristics, such as eye color, intelligence etc.

DNA DNA is a double helix composed of two intertwined nucleotide chains oriented in opposite directions. The double helix composed of building block called nucleotides

DNA Each nucleotides consist : Phosphate group Deoxyribose sugar molecule One of four different nitrogenous bases either Purines - Adenine and Guanine, or Pyrimidines -Cytosine and Thymine)

DNA The functional units of DNA are genes. A gene is a segment of DNA that can be copied to make RNA. The nucleotide sequence in RNA is translated into the amino acid sequence of a protein. Proteins are the main determinants of the basic structural and physiological properties of an organism.

Protein synthesis DNA is duplicated before a cell divides A process called replication

Protein synthesis Genes are transcribed into RNA (transcription).   Genes are transcribed into RNA (transcription). Non-coding parts are removed called mRNA Transported out of the nucleus Outside the nucleus, the proteins are built (translation).

Mutation Mutations Inherited Acquired Carrier or diseased Caused by radiation, toxins, diet, infections

Mutation Variation within a species may be from hereditary variation, environmental variation, or both. The newly created offspring can then be mutated. Mutation means that the elements of DNA are a bit changed. The effect of mutation depends on both the mutation and its location

Mutation Errors in the replication of DNA have been postulated as being responsible for the mutations seen in conditions such as Huntington's disease2 and myotonic dystrophy. Errors in recombination are responsible for mutations called translocations, such as occur in leukemias and other cancers. Normal recombination produces genetic variation by the exchange of genetic material between paired chromosomes.

Mutation Mutations can arise through a variety of mechanisms range from changes in a single nucleotide to the loss, duplication or rearrangement of entire chromosomes. When a gene contains a mutation, the protein encoded by that gene will be abnormal and sometimes changes are insignificant

Mutation Some mutations are silent; they affect neither the structure of the encoded protein nor its function. Other mutations result in an altered protein. Certain chemicals produce DNA damage that leads to mutation, tobacco smoke, certain dyes and chemotherapeutic agents

Alleles Genes come in pairs, with one copy inherited from each parent. Many genes come in a number of variant forms, known as alleles. A dominant allele prevails over a normal allele. A recessive gene becomes apparent if its counterpart allele on the other chromosome becomes inactivated or lost.

Dominant genes In dominant genetic disorders, if one affected parent has a disease-causing allele that dominates its normal counterpart, each child in the family has a 50-percent chance of inheriting the disease allele and the disorder.

Recessive genes In diseases associated with altered recessive genes, both parents - though disease-free themselves- carry one normal allele and one altered allele. Each child has one chance in four of inheriting two altered alleles and developing the disorder; one chance in four of inheriting two normal alleles, two chances in four of inheriting one normal and one altered allele, and being a carrier like both parents.

Genetic disorders Chromosome Abnormalities A karyotype is a display of the chromosomes of a single cell.

Genetic disorders Single-Gene Disorders Some disorders due to a single gene to be altered or missing. Example is sickle-cell anemia. Mutations in the beta-globin gene cause blood cells to become a sickle shape. The sickle cell easily get clogged in the narrow passages.

Genetic disorders Multifactorial Disorders Multifactorial disorders result from mutations in multiple genes, often coupled with environmental causes. The complicated bases of these diseases make them difficult to study and to treat. Heart disorder, diabetes and cancer are examples of this type of disorder.

What is the relationship between genes and cancer? All cancer is genetic It is triggered by altered genes. A small portion of cancer is inherited A mutation carried in reproductive cells, passed on from one generation to the next, and present in cells throughout the body.

What is the relationship between genes and cancer? Most cancers come from random mutations that develop in body cells during one's lifetime - either as a mistake when cells are going through cell division or in response to injuries from environmental agents such as radiation or chemicals.

What is the relationship between genes and cancer? Cancer usually arises in a single cell. The cell's progress from normal to malignant to metastatic appears to follow a series of distinct steps, each one controlled by a different gene or set of genes. Several types of genes have been implicated. Oncogenes normally encourage cell growth; when mutated or overexpressed Tumor-suppressor genes normally restrain cell growth

What is Genetic Testing? Means a laboratory test of a person’s genes or chromosomes for abnormalities, defects, or deficiencies, including carrier status, that are linked to physical or mental disorders or impairments or a susceptibility to them.

Genetic testing How do they test? Testing for extra chromosomes Testing of DNA Testing for a protein

Genetic testing In clinical research programs, doctors make use of genetic tests : early detection (familial adenomatous polyposis) genes prompt close surveillance for colon cancer); diagnosis (different types of Leukaemia can be distinguished); prognosis (the product of a mutated p53 tumour suppressor gene) flags cancers that are likely to grow aggressively); and treatment (antibodies block a gene product that promotes the growth of breast cancer).

Genetic testing Methods for detecting genetic abnormalities, depend upon the size and nature of the mutation. Some techniques are applied to test for chromosomal DNA itself, some to the RNA copies and some to the protein product of the gene

Genetic testing Single base pair mutations can be identified by any of the following methods: Direct sequencing, which involves identifying each individual base pair, in sequence, and comparing the sequence to that of the normal gene This tends to be a labour-intensive method reserved for previously unidentified mutations or rare mutations of a common disease (such as cystic fibrosis), when other methods do not detect the disease that is clinically suspected.

Genetic testing Larger mutations involve the deletion, rearrangement, expansion or duplication of parts of genes, entire genes or multiple genes: A number of strategies use the polymerase chain reaction to amplify specifically the region involving the mutation.

Genetic testing Results of genetic tests could show: Genetic diseases Will get or already has the disease Genetic predispositions Could, maybe, might get the disease

Genetic Tests Find Mutations, NOT Disease Women with the BRCA1 breast cancer susceptibility gene have an 80-percent chance of developing breast cancer by the age of 65. The risk is high but not absolute Family members who negative for the BRCA1 mutation are not exempt from breast cancer risk over time, they can acquire breast cancer-associated genetic changes at the same rate as the general population

Technical Concerns Before predictive gene tests become generally available, specialists and society must come to grips with major technical, ethical, and economic concerns. If widespread gene testing becomes a reality, it will be necessary to develop tests that are simple, cost-effective, and accurate.

Technical Concerns Testing thousands to millions of people will require many new labs and personnel as well as more genetic counselors. Widespread gene testing will require many health care providers have a basic understanding of genetic principles in order to interpret the tests.

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