BIOL311 Lectures Topic 1 Full Notes.pdf

BIOL 311: Principles of Genetics In this course, we’ll focus on: Gaining an understanding of genetic principles Applying these principles to solve problems Developing a vocabulary and context for understanding genetics Classical Genetics Molecular Gene...

BIOL 311: Principles of Genetics In this course, we’ll focus on: Gaining an understanding of genetic principles Applying these principles to solve problems Developing a vocabulary and context for understanding genetics Classical Genetics Molecular Genetics Topic 7: DNA replication and PCR Topic 1: Single gene inheritance Topic 8: DNA variation and sequencing Topic 2: Independent assortment Topic 9: Gene structure, transcription, of genes translation Topic 3: Genetic linkage Topic 10: Prokaryotic gene regulation Topic 4: Gene interactions Topic 11: Eukaryotic gene regulation Topic 5: Recombination and large Topic 12: Cloning, restriction mapping, chromosomal rearrangements and Crispr Topic 6: Bacterial and viral genetics Topic 13: Genetics of development Tips for success in Biology 311 ATTEND CLASS and BE ENGAGED (and keep up!) Textbook Readings (Achieve adaptive reading/quizzes) Practice problems and assignments (more than once if possible!) Prepare for labs in advance - read and understand purpose Check D2L often (at least every few days; additional resources posted)  Think about how YOU learn best Time of day? Location? (not in bed) Active studying throughout term weekly lecture summaries rewriting notes/key points flash cards/self testing and reflecting Find a study partner(s) Re-reading notes/text is quick and comfortable, but passive and least helpful  What is Genetics? Classical Genetics – Deals with inheritance of traits; “Transmission genetics” discovered by Gregor Mendel Molecular Genetics – study of DNA and RNA structure, function, and molecular control of gene expression Evolutionary/Population Genetics – interaction of genes and gene pools and the environment  Some Terms Gene – a hereditary unit of information (simple definition) Gene Locus – the position of a gene on the chromosome Allele – one of two (or more) versions of a gene that differs in sequence and exists at the same loci Genotype – the combinations of alleles for any gene Phenotype – the observable characteristics, as determined by the geneotype Wild type – The most prevalent phenotype in a population under natural conditions Mutant (phenotype) – a deviation to the wild-type phenotype as a result from an allelic change in DNA sequence Wild type – The most Dominant – The phenotype prevalent phenotype in a observed in heterozygous population under natural individuals (i.e. genotype conditions includes both allele variants) VS Mutant (phenotype) – a Recessive – The phenotype deviation to the wild-type observed only in individuals phenotype as a result from that are homozygous for the an allelic change in DNA recessive allele variant sequence  The Molecular Basis for Dominance Gregor Mendel tested traits with only 2 phenotypes – “Dominant” and “recessive” refer to the phenotypes – whether one allele is dominant over the other is determined by the proteins produced by each of the alleles Scenario 1: Only 10 units of protein are required to produce the wild-type phenotype 10 0 0 + wild-type allele + m m m mutant allele + + m 10 10 0  The Molecular Basis for Dominance A wild-type phenotype is produced when an organism has two copies of the wild- type allele, or when one copy is sufficient to meet the protein requirements Mutant alleles can be: – Loss of function: significant decrease or complete loss of functional gene product – Gain of function: gene product acquires a new function or expression increased above wild-type activity Scenario 1: Only 10 units of protein are required to produce the wild-type phenotype 10 0 0 + wild-type allele + m m m mutant allele + + m 10 10 0 Mutation is recessive, loss of function  The Molecular Basis for Dominance A wild-type phenotype is produced when an organism has two copies of the wild- type allele, or when one copy is sufficient to meet the protein requirements Mutant alleles can be: – Loss of function: significant decrease or complete loss of functional gene product – Gain of function: gene product acquires a new function or expression increased above wild-type activity Scenario 2: A minimal number required for wild-type phenotype (i.e. gene is off) 1 20 20 + wild-type allele + m m m mutant allele + + m 1 1 20 Mutation is dominant, gain of function  The Molecular Basis for Dominance Incomplete dominance is common, where heterozygous individuals display intermediate phenotypes between either homozygous type Scenario 3: 20 units are required to produce the wild-type phenotype, but fewer units will produce an intermediate 10 0 0 + wild-type allele + m m m mutant allele + + m 10 10 0 Mutation is loss of function, not completely recessive  The Molecular Basis for Dominance Codominance results when there is detectable expression of both alleles in the heterozygotes Scenario 4: 10 units are required to produce the wild-type or mutant phenotype 10 10 10 + wild-type allele + m m m mutant allele + + m 10 10 10 Mutation is codominant  Dominance relationships of ABO Alleles More than one pattern of dominance may exist between different alleles of a gene The ABO blood type has 4 different phenotypes resulting from combinations of 3 alleles: IA, IB, and i – IA and IB produce different antigens and are codominant with each other, but completely dominant over i which makes no antigens Type O Type A Type B Type AB Genotype i/i IA/IA or IA/i IB/IB or IB/i IA/IB Antibodies anti-A anti-B anti-A none anti-B  The Molecular Basis of Mendelian Inheritance Patterns Dominance and Recessiveness Revisited Recessiveness: Recessiveness is observed in mutations in genes that are functionally haplosufficient (+/m, where m is a mutated allele). The mutated allele is the recessive allele. Dominance: In genes that are haploinsufficient, in a heterozygote (+/M), the single wild-type allele (+) cannot provide enough product for normal function. The mutated allele (M) is the dominant allele.  Nomenclature Single letter - denotes mutant phenotype (or recessive, if mutant unknown) Upper case denotes dominant allele Lower case denotes recessive allele Ideally should be italicized (or underlined) Slashes indicate alleles for gene(s) on homologous chromosomes Semicolons indicate genes on non-homologous chromosomes A/a;B/b Ab/aB AB/ab Single Gene Inheritance (Review from BIOL 243) Chapter 2 Many traits are coded for by a single gene mutations in the gene result in an observable change in the phenotype Patterns of single gene inheritance first described by Gregor Mendel Gregor Mendel (1822-1884) Garden pea, Pisum sativum Examined seven traits through crossing and selfing All discontinuous traits (“either/or”) Mendel’s Law of Equal Segregation Started with PURE LINES of pea plants One trait: flower colour – monohybrid cross Parental (P0) purple flowers X white flowers First Filial (F1) All purple = dominant Second Filial (F2) 3/4 purple : 1/4 white 3:1 Another trait: seed colour yellow seeds X green seeds Not all yellow in F2 generation are the same Mendel’s Model Genes are in pairs – gene may have different forms (ALLELES) Gametes contain only one allele of each gene pair Equal Segregation – Half of gametes carry one allele of gene pair, half carry the other allele - MENDEL’S FIRST LAW Random fertilization Phenotype vs. Genotype Phenotype - What you see (e.g. yellow seeds) Genotype - Allele combination (symbol indicates mutant OR recessive phenotype) use same letter for same gene, different case for different alleles (basic) P0 yellow X green G/G g/g F1 yellow G/g F2 yellow green G/G G/g g/g  Punnett Square P0 G/G X g/g F1 G/g F2  Test Cross Cross used to determine the genotype of an individual that is expressing a dominant phenotype G/- = yellow phenotype cross to the TESTER (homozygous recessive) if G/G if G/g G/G x g/g G/g x g/g ↓ ↓ all G/g (yellow) 1/2 G/g (yellow) : 1/2 g/g (green) 1:1 Mendel’s Law of Equal Segregation G g G g  Parts of a chromosome Centromere Telomere P arm Q arm Telomere metacentric acrocentric telocentric  n, the ploidy number n refers to the number of sets of chromosomes (not the total number) n haploid; one set 2n diploid; two sets 3n triploid etc. Chromosomes  Chromosome vs. Chromatid Before mitosis or meiosis, DNA replication occurs to form dyad one chromosome, one chromatid S phase one chromosome, two sister chromatids mitosis/meiosis II one chromosome, one chromatid Sister chromatids have the exact same alleles! Non-sister chromatids can be same (homozygotes) or different (heterozygotes) Cell Division: Mitosis Figure 2-8 Key stages of meiosis and mitosis Mendel’s Law of Equal Segregation (refined)  Chromosomal Theory of Inheritance (1902-03) Sutton and Boveri looked at separation of chromosomes during meiosis under microscope Proposed that Mendel’s “particles” were associated with chromosomes Morgan was a skeptic, but later proved them right Sex linkage non-autosomes = sex chromosomes if one sex does not have a pair of similar sex chromosomes, the other does Homogametic: matching pair of sex chromosomes (ex. XX) Heterogametic- no matching pair (ex. XY) Testing for sex linkage – Reciprocal Cross Reciprocal Cross X+/X+ x Xw/Y Xw/Xw X+/Y P0 ♀ ♂ Alleles w = mutant (white) + = wild-type (Red) X+/Xw x X+/Y X+/Xw Xw/Y F1 ♀ ♂ X+/X+ X+/Xw F2 ♂ ♂ ♀ X+/Y Xw/Y X+/Xw Xw/Xw X+/Y Xw/Y  Human Pedigree Analysis We can’t ethically test cross humans, so we have to look back through families trees and medical records: pedigree analysis Propositus – first member of a family who comes to the attention of a geneticist (usually has a disease) May not see 3:1 and 1:1 ratios (small family size), but can look for patterns suggesting dominance and sex-linkage  Autosomal Recessive Pedigree 1. Disease often shows up from unaffected parents (carriers) 2. If both parents have the trait, all children will have it 3. Males and females have equal likelihood of showing the trait (although totals might not be equal)  Autosomal Dominant Pedigree 1. No skipping of generations – each affected individual must have at least one affected parent 2. Either males and females can transmit the mutant allele to both sons and daughters with equal probability 3. Two affected parents can produce unaffected children, but two unaffected parents can never have affected children Recessive pedigree example- Rh factor Rh+ dominant Rh- recessive  Rare disease vs. Polymorphism Polymorphisms (i.e. Rh factor) – carriers are common in population Rare diseases – carriers not common THEREFORE: FOR RARE DISEASES ASSUME NEW INDIVIDUALS COMING INTO FAMILY (spouses/mates) ARE NOT CARRIERS – unless other info suggests otherwise  X-linked recessive rare disease 1. More males than females affected 2. If father is affected, none of his offspring will be affected (assuming mom not carrier) X+/X+ Xm/Y X+/Xm X+/Y 3. All male offspring from an affected female will be affected Xm/Xm X+/Y X+/Xm Xm/Y  X-linked dominant rare disease X+/X+ XM/Y All daughters of an affected male will be affected No sons of affected male with be affected – unless mother is also affected/carrier XM/X+ X+/Y An affected female (assuming heterozygous) will transmit the affected allele to male and female offspring with equal probability XM/X+ X+/Y XM/Y X+/X+ X+/Y XM/X+ Practice Question A man’s paternal grandfather has galactosemia, a rare autosomal recessive disease caused by the inability to process galactose, leading to muscle, nerve and kidney malfunction. The man married a woman whose sister had galactosemia. The woman is now pregnant with their first child. a) Draw the pedigree as described b) What is the probability that this child will have galactosemia? c) If the first child does have galactosemia, what is the probability that a second child will have it? A man’s paternal grandfather has galactosemia, a rare autosomal a) recessive disease caused by the inability to process galactose, leading to muscle, nerve and kidney malfunction. The man married a woman whose sister had galactosemia. The woman is now pregnant with their first child. a) Draw the pedigree as described b) What is the probability that this B) prob for child = (prob dad G/g) x (prob mom G/g) x (prob g/g) child will have galactosemia? = 1/2 x 2/3 x 1/4 c) If the first child does have = 2/24 = 1/12 galactosemia, what is the probability that a second child C) now know both parents are carriers, so probability now just 1/4 will have it?  Things to know from Topic 1 1) Inheritance patterns for monohybrid and sex-linked crosses - Expected ratios (genotypic and phenotypic) 2) Why you do a test cross and expected ratios 3) Mendel’s Law of equal segregation. How it relates to meiosis 4) Similarities and differences between mitosis and meiosis 5) Recognize Autosomal Recessive, Autosomal Dominant, Sex- Linked Recessive and Sex-Linked Dominant Pedigrees 6) Determine genotypes of individuals based on pedigrees 7) Determine probabilities of phenotypes or genotypes of individuals based on pedigrees