Pharmacogenetics and Pharmacoepidemiology Course Coordinator Jamaluddin Shaikh, Ph.D. Lecture 1 September 09, 2013 Introduction to pharmacogenetics

Chromosomes Diploid genome Chromosomes contain genetic material. Almost every cell type carries 23 pairs of chromosomes. Diploid genome: Most cells are diploid because they carry pairs of chromosomes. Half of each pair is inherited from the mother and the other half is inherited from the father. Diploid genome

Chromosomes Haploid genome: The gametes (sperm and egg) carry 23 chromosomes that are not paired. They are considered haploid since they carry only one set of chromosomes.

Chromosomes Chromosome Structure: Each chromosome is made up of DNA tightly coiled many times around proteins called histones that support its structure. Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or “arms.” The short arm of the chromosome is labeled the “p arm.” The long arm of the chromosome is labeled the “q arm.” The location of the centromere on each chromosome gives the chromosome its characteristic shape.

Chromosomes

DNA DNA (deoxyribonucleic acid) Composition: DNA is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA. The information in DNA is stored as a code made up of four chemical bases: A (adenine), G (guanine), T (thymine), and C (cytosine). Nucleotide bases are linked together in a structure called the double helix. Bases on opposite strands are always matched A-T and C-G.

DNA DNA Composition

GENE Gene Structure: Genes are made up of segments of DNA and are arranged on the chromosome. Generally, one gene codes for one protein.

GENE Gene Structure: Most genes are divided into coding regions called exons, and non-coding regions called introns.

GENE Gene Structure: Regulatory regions that flank each gene can influence the expression or activity of each gene. The regulatory non coding region preceding the coding region of the gene is called the promoter.

Human Genome

GENE How do genes direct the production of proteins? The journey from gene to protein is complex and it consists of two major steps: transcription and translation. Together, transcription and translation are known as gene expression. Transcription of Genes: Transcription involves RNA polymerase enzyme which unravels and unzips DNA helix in the cell's nucleus. That leads to the synthesis of messenger RNA (mRNA) strand using the gene's DNA as a template. The mRNA strand is synthesized by sequential addition of nucleotides that are complementary to those on the DNA template strand.

Chromosomes Transcription of Genes

GENE Translation into Protein: A newly synthesized mRNA strand is transported out of the nucleus where it is bound by ribosomes. In the ribosomes, transfer RNAs bind to the mRNA strand in a sequence-specific manner, each carrying an amino acid. As the tRNAs bind to the mRNA, their respective amino acids are bonded together to form a growing amino acid (or polypeptide) chain. A mature, functional protein is formed when the amino acid chain is complete.

Chromosomes Translation into Protein

Chromosomes Codons:

GENE Codons: The genetic code guides the formation of functional proteins. Each amino acid is encoded by 3 nucleotides. This set of 3 nucleotides is called a codon. Proteins are formed by chains of amino acids, and synthesis continues until the ribosome encounters a “stop” codon (a sequence of three bases that does not code for an amino acid).