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Today… Genome 351, 15 April 2013, Lecture 5 •Meiosis: how the genetic material is partitioned during the formation of gametes (sperm and eggs) •Probability: -the product rule -the sum rule •Independent assortment of nonhomologous chromosomes during meiosis Meiosis: the formation of gametes DNA Replication DNA Recombination (crossing over) Meiotic Division 1 • Copied chromosomes (sister chromatids) stay joined together at the centromere. • Homologous chromosomes pair up and physically join at sites of recombination • Proteins pull the two homologs to opposite poles Meiotic Division 2 • Proteins pull the two sister chromatids to opposite poles • Each gamete gets a copy of only one homolog (usually a maternal-paternal hybrid). Mitosis vs. Meiosis 1m 1p 2 x 1m 2 x 1m 2 x 1p 2 x 1m 2 x 1p 1m 1p 1m 1p 1m 1m 1p 1m 1p exact copies 2 x 1m/p 2 x 1m/p 2 x 1m/p 1m 1p DNA Replication 2 x 1p DNA Recombination 2 x 1p/m 2 x 1p/m 2 x 1p/m 1p/m 1m/p 1p Meiotic Division I Crossovers hold the homologues together until all of the chromosomes are attached to the spindle Meiotic Division I Crossovers hold the homologues together until all of the chromosomes are attached to the spindle The homologues then separate from one another, exchanging corresponding portions as they do so Meiotic Division II The two daughter cells from meiotic division I go directly into meiotic division II Sister chromatids separate during meiotic division II Mitosis vs. Meiosis • One round of DNA synthesis with one cell division • Two genetically identical daughters • Sister chromatids segregate • Homologs do not line up or separate • Homologs do not exchange corresponding segments (no crossing over) • Final products are diploid (2n) Probability in genetics Probability is important in genetics Needed for… - testing hypotheses - mapping disease genes - genetic counseling Pedigree of a family segregating phenylketonuria (PKU) What can we infer from the pedigree? Use of the Product and Sum rules A couple has a first child who tests positive for PKU. What can you infer about their genotypes? What is the probability that their next child will have PKU? What is the chance the next child, if he or she is not affected, will be a carrier? Following the fate of the PAH gene in a PAH+/heterozygote during meiosis PAH+ 2 copies PAH+ 2 copies PAH+ PAH+ PAH+ PAH+ PAH+ PAH+ PAH+ PAHDNA Replication 2 copies PAHDNA Recombination 2 copies PAHPAHPAHPAHPAHPAHPAH- PAH+ PAH+ PAH- PAH- Following the fate of the PAH gene in a PAH+/heterozygote during meiosis PAH+ 2 copies PAH+ 2 copies PAH+ PAH+ PAHPAH+ PAHPAH+ PAH- PAHDNA Replication 2 copies PAHDNA Recombination 2 copies PAHPAH+ PAHPAH+ PAHPAH+ PAH- PAH+ PAH- PAH+ PAH- Genetic accounting sperm What are the possible genotypes and phenotypes of the children of parents who are both phenylketonuria carriers? eggs Product rule PAH+/- PAH+/- PAH-/- Probability of sperm Product Rule: The probability of 2 or more independent events occurring simultaneously What is the probability that their next child will have PKU? eggs PAH-/-? ½ PAH+ ½ PAH½ PAH+ PAH+ PAH+ PAH+ PAH- ½ PAH- PAH+ PAH- PAHPAH- Sum rule PAH+/- What is the chance the next child, if he or she is not affected, will be a carrier? eggs PAH+/- PAH-/- ½ PAH+ ½ PAH- sperm Sum Rule: The probability of an event that can occur in 2 or more ways = sum of the separate probabilities Probability of PAH+/-? ½ PAH+ PAH+ PAH+ ½ PAH- PAH+ PAH- PAH+ PAHPAHPAH- Punnett Square Execution Determine types of gametes from each parent Combine each type of female gamete with each male gamete Advantages of Punnett Square Organized and systematic Gives all possible combinations of genotypes automatically Disadvantages of Punnett Square Slow and labor intensive, especially for complex genotypes (e.g., AaBbCc X AabbCc) Using the product and sum rules Example: Albinism… a = no pigment What is the probability that III-1 will be albino? Two events necessary: II-3 must be Aa and they must have aa child Independent assortment of nonhomologous chromosomes during meiosis What happens to non-homologous chromosomes during meiosis? Independent assortment of nonhomologous chromosomes during meiosis Two equally probable arrangements: 1m 2m 1m 2m 1m 1 m 2m 2m 1p 1p 2p 1m 2m 1p 2p 1p 1p 2p 2p 2p 1m 2p 1p 2m 1p 1p 2m 2m 1m 2p 1m 2p Meiosis and independent assortment of nonhomologous chromosomes can create many different types of gametes Examples: 1 pair of homologous chromosomes gives 2 types of gametes (21 = 2) 2 pairs of homologous chromosomes gives 4 types of gametes (22 = 4) n pairs of homologous chromosomes gives 2n types of gametes 23 pairs of homologous chromosomes gives 223 (8 million) types of gametes An example of independent assortment • Following the fate of genes on different (nonhomologous) chromosomes – Cystic fibrosis on chromosome 7 – A gene that influences ABO blood types on chromosome 9 Some background on ABO blood groups A red cells = A antigen = B antigen B red cells AB red cells O red cells The ABO (I) gene There are 3 different versions (alleles) of the I gene: I alleles IA A adds A sugar to red cell surface IB B adds B sugar to red cell surface i adds no sugar to red cell surface The ABO gene - dominance relationships IA is dominant to i IA/IA or IA/i - A blood type IB is dominant to i IB/IB or IB/i - B blood type i is recessive i/i - O blood type IA is co-dominant with IB IA/IB - AB blood type The I gene lies on chromosome 9q34 Independent assortment of genes on nonhomologous chromosomes Gametes formed from a CFTR+/- IA/i double heterozygote: CFTR+ CFTR- CFTR- IA CFTR+ IA i CFTRi CFTR+ IA i CFTR- IA CFTR+ i CFTR+ CFTR+ CFTR-CFTR-CFTR-CFTR- CFTR+ CFTR+ i IA i IA IA i i IA Gametes that arise from a CFTR+/IA/i double heterozygote: CFTR+ IA CFTR+ IA 1/4 CFTR- i CFTR- i 1/4 CFTR- IA CFTR- IA 1/4 CFTR+ i CFTR+ i 1/4 Possible genotypes and phenotypes from a mating of CFTR+/- IA/i double heterozygotes Eggs Sperm CFTR+ IA CFTR- CFTR+ i i CFTRIA CFTR+ C+/+ IA IA/IA C+/IA/i C+/+ IA/i IA/IA CFTRi C+/IA/i C-/i/i C+/i/i C-/IA/i CFTR+ C+/+ i IA/- C+/i/i C+/+ i/i C+/IA/i CFTR- C+/IA IA/IA C-/IA/i C+/IA/i C-/IA/IA C+/- What genotypes give CF and A blood type? What genotypes give nonCF and A blood type? What genotypes give nonCF and O blood type? What genotype gives CF and O blood type? 1/4 1/4 1/4 1/4 CFTR+ IA CFTRi CFTR+ i CFTRIA C+/IA/i C+/+ IA/i C+/IA/IA +/+ + C CFTR 1/4 IA/IA IA CFTR 1/4 i C+/IA/i C-/i/i C+/i/i C-/IA/i + CFTR 1/4 i C+/+ IA/- C+/i/i C+/+ i/i C+/IA/i CFTR 1/4 IA C+/IA/IA C-/IA/i C+/IA/i C-/IA/IA 9 N, A 3 N, O 3 CF, A 1 CF, O