Introduction to Human Genetics Chapter One

What is DNA? Deoxyribonucleic Acid: String of nucleotides deoxyribose Nucleotides made up of three parts: deoxyribose (a sugar) OH HO-CH2 + P – – = O - phosphate + cyclic amine (base) N

Nucleotide OH O-CH2 P – – = O - N

DNA Specific Bases Sugar-Phosphate Backbone (negatively charged) N - O O-CH2 P – – = O - N Specific Bases O-CH2 P – – = O - N O O-CH2 P – – = - N Sugar-Phosphate Backbone (negatively charged)

The Five Bases A = Adenine T = Thymine G = Guanine C = Cytosine RNA only: U = Uracil (replaces T)

Structures of Bases Pyrimidines T U C Purines A G O NH2 O CH3 N N N O

DNA T A Sequence of DNA is order of the bases attached to backbone C - P – – = O - T - O-CH2 P – – = O A - O-CH2 Sequence of DNA is order of the bases attached to backbone P – – = O C - O O-CH2

Double Helix Sugar-Phosphate backbone is on outside Bases are inside - Hydrogen-bonding to opposing base on opposite strand Forming Base Pairs

Base Pairing Experiments showed: Therefore… Two strands were always same distance apart Percentages of A always matched T, and G always matched C Therefore… A Purine must always be base paired to a Pyrimidine A = T, and G = C Strands must be complementary =

Summary of DNA String of Nucleotides deoxyribose Sugar-Phosphate backbone 4 Bases: A, G are Pyrimidines T, C are Purines A = T G = C Two complementary strands (double helix) =

Central Dogma dog·ma P Pronunciation Key (dôg ma) n. pl. dog·mas or dog·ma·ta 1. A doctrine or a corpus of doctrines relating to matters such as morality and faith, set forth in an authoritative manner by a church. An authoritative principle, belief, or statement of ideas or opinion, especially one considered to be absolutely true.

Central Dogma DNA RNA Protein Transcription Translation

Transcription initiation elongation termination RNA polymerase Double Stranded DNA “Promoter” opens initiation elongation termination single stranded mRNA

Translation 4 Nucleotides 20 amino acids ...AGAGCGGAATGGCAGAGTGGCTAAGCATGTCGTGATCGAATAAA... AGAGCGGA.AUG.GCA.GAG.UGG.CUA.AGC.AUG.UCG.UGA.UCGAAUAAA MET.ALA.GLU.TRP.LEU.SER.MET.SER.STOP 4 Nucleotides 20 amino acids 1 base codon - 41 = 4 possible amino acids . 2 base codon - 42 = 16 possible amino acids 3 base codon - 43 = 64 possible amino acids

Translation amino acid tRNA single stranded mRNA } Codon (3 bases)

The Genetic Code UUU UUC UUA UUG CUU CUC CUA CUG AUU AUC AUA AUG GUU GUC GUA GUG UCU UCC UCA UCG CCU CCC CCA CCG ACU ACC ACA ACG GCU GCC GCA GCG UAU UAC UAA UAG CAU CAC CAA CAG AAU AAC AAA AAG GAU GAC GAA GAG UGU UGC UGA UGG CGU CGC CGA CGG AGU AGC AGA AGG GGU GGC GGA GGG Phe Leu Val Ser Pro Thr Ala Tyr Stop His Gln Asn Lys Asp Glu Cys Arg Ser Gly Stop Trp Ile Met

Translation Note: Actually a different tRNA for each different codon

Proteins Sequence Structure Function Protein Sequence = order of the amino acids Sequence Structure Function

Central Dogma Summary DNA is in the nucleus of each cell DNA encodes for RNA (transcription) RNA encodes for Proteins (translation) DNA and RNA are made of nucleotides Protein is made of amino acids A protein’s function is determined by it’s structure, which is determined by it’s sequence Therefore…DNA encodes protein function

What is a gene anyway? A gene is a small piece of DNA It begins with a promoter This is region of sequence that tells RNA polymerase “start here” Also regulates amount of mRNA that is made Includes Introns and Exons Introns are removed during transcription Exons are the parts of the sequence that become mRNA Also, gene has regulatory regions

Gene Structure mRNA protein

One gene = one protein Only not really: Splice variants = form different proteins Different alleles = different versions of the same protein Polymorphisms; may change protein sequence or regulation of protein Mutations may destroy a protein, or change it’s normal function or expression

Genetic variance: Allele: Alternative form of one gene, usually form same protein, with slight changes, but same function Polymorphism: Usually a silent change (something that doesn’t affect the protein), that is often common in population Mutation: A change in the DNA sequence that will change the protein’s function or regulation, usually in a detrimental way

Sequence vs. Expression Genetic variances can affect: Sequence of the gene May change the sequence of the protein May be “silent” Level the gene is expressed Amount of protein that will be made Where a gene is expressed What cell type What tissue What time point in development

Chromosomes Chromosomes can carry thousands of genes Made of DNA and proteins Human have 22 pairs of autosomal chromosomes 1 is the largest, 22 is the smallest Humans have 1 pair of sex chromosomes XY is male, XX is female X inactivation in females

How are genes inherited? Genes are carried in the DNA DNA is condensed into chromosomes Each individual has two copies of every chromosome Sex cells (sperm or eggs) each have one copy of every chromosome Mating leads to one copy of every chromosome coming from one parent and other copy coming from the other parent Variances are mixed in offspring

Traits Any distinguishing feature that can be measured Quantitatively (ex. height, weight) Qualitatively (ex. disease status) Inherited Traits Completely genetic Non-inherited Traits Completely Environmental Complex Traits Partially Genetic, partially environmental Ask class what are examples of genetic (gender, fingerprints) vs. non-genetic traits (racism)?

Complex Traits Disorder that is proven heritable, yet has no clear mode of inheritance Doesn’t follow Mendel’s laws More than one gene Interaction between genes Interaction between gene(s) and environment

Why Common Complex Disorders and Rare Mendelian Disorders? Evolution can act upon a single detrimental gene negative selection Gene functions that are good for some things, but can be harmful in excess ex: rational fear vs. anxiety disorders Normal alleles only predisposing other mutations/environment present

Genotype vs. Phenotype Genotype = combination of alleles individual is carrying Genes (which versions) Phenotype = measurable traits individual shows Final Product

Applications: Selection Evolution Forensics Medical Care First use of genetics What are some examples? Evolution Tracing origins Forensics Medical Care Studying, treating, curing diseases

Next Class: Read Chapter Three Homework – Chapter One Problems; Review: 1, 2, 4 Applied: 3, 4, 11, 14