Introduction to Genetic

Dr Rosline HassanDepartment of HaematologySchool of Medical SciencesUniversity Sains Malaysia

Table of contentsChromosomeDNAProtein synthesisMutationGenetic disorderRelationship between genes and cancerGenetic testingTechnical 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.

ChromosomeEach 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.

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

DNAEach nucleotides consist :

Phosphate groupDeoxyribose sugar moleculeOne of four different nitrogenous bases either Purines - Adenine and Guanine, or Pyrimidines -Cytosine and Thymine)

DNAThe 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 synthesisDNA is duplicated before a cell dividesA process called replication

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

 

Mutation Mutations

InheritedCarrier or diseased

Acquired Caused by radiation, toxins, diet, infections

MutationVariation 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

MutationErrors 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.

MutationMutations 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

MutationSome 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 genesIn 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 genesIn 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 disordersChromosome AbnormalitiesA karyotype is a display of the chromosomes of a single cell.

Genetic disordersSingle-Gene DisordersSome 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 disordersMultifactorial DisordersMultifactorial 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 geneticIt is triggered by altered genes. A small portion of cancer is inheritedA 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 overexpressedTumor-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 testingHow do they test?

Testing for extra chromosomesTesting of DNATesting for a protein

Genetic testingIn 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); andtreatment (antibodies block a gene product that promotes the growth of breast cancer).

Genetic testingMethods 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 testingSingle 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 geneThis 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 testingLarger 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 testingResults of genetic tests could show:

Genetic diseasesWill get or already has the disease

Genetic predispositionsCould, 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 ConcernsTesting 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.

THANK YOU