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 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). (crossing over)

Mitosis vs. Meiosis 1m1m 1p1p 2 x 1 m 2 x 1 p 1m1m 1p1p 1m1m 1p1p 1m1m 1p1p 1m1m 1p1p 2 x 1 m 2 x 1 p exact copies DNA Replication DNA Recombination 1m1m 1p1p 2 x 1 m 2 x 1 p 2 x 1 m/p 2 x 1 p/m 1m1m 1p1p 1 m/p 1 p/m 2 x 1 m/p 2 x 1 p/m 2 x 1 m/p 2 x 1 p/m

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 I Crossovers hold the homologues together until all of the chromosomes are attached to the spindle

The two daughter cells from meiotic division I go directly into meiotic division II Sister chromatids separate during meiotic division II Meiotic Division II

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) Mitosis vs. Meiosis

Probability in genetics

Probability is important in genetics - testing hypotheses -mapping disease genes -genetic counseling Needed for…

Pedigree of a family segregating phenylketonuria (PKU) What can we infer from the pedigree?

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? Use of the Product and Sum rules

DNA Replication DNA Recombination 2 copies PAH + 2 copies PAH - 2 copies PAH + 2 copies PAH - PAH + PAH - PAH + PAH - PAH + PAH - PAH + PAH - Following the fate of the PAH gene in a PAH +/- heterozygote during meiosis

DNA Replication DNA Recombination PAH + PAH - PAH + PAH - 2 copies PAH + 2 copies PAH - 2 copies PAH + 2 copies PAH - PAH + PAH - PAH + PAH - PAH + PAH - PAH + PAH - PAH + PAH - PAH + PAH - PAH + PAH - Following the fate of the PAH gene in a PAH +/- heterozygote during meiosis

Genetic accounting What are the possible genotypes and phenotypes of the children of parents who are both phenylketonuria carriers? eggs sperm

Product rule PAH +/- PAH -/- What is the probability that their next child will have PKU? PAH + eggs sperm ½ PAH + ½ PAH - ½ PAH + ½ PAH - PAH + PAH - PAH + PAH - Probability of PAH -/- ? Product Rule: The probability of 2 or more independent events occurring simultaneously

Sum rule PAH +/- PAH -/- What is the chance the next child, if he or she is not affected, will be a carrier? PAH + eggs sperm ½ PAH + ½ PAH - ½ PAH + ½ PAH - PAH + PAH - PAH + PAH - Probability of PAH +/- ? = sum of the separate probabilities Sum Rule: The probability of an event that can occur in 2 or more ways

Punnett Square 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 Slow and labor intensive, especially for complex genotypes (e.g., AaBbCc X AabbCc) Disadvantages of Punnett Square Execution

Two events necessary: II-3 must be Aa and they must have aa child Example: Albinism… a = no pigment What is the probability that III-1 will be albino? Using the product and sum rules

Independent assortment of nonhomologous chromosomes during meiosis What happens to non-homologous chromosomes during meiosis?

1m1m 1p1p 2m2m 2p2p 1m1m 2m2m 1p1p 2p2p 1m1m 2m2m 1m1m 2m2m 1p1p 2p2p 1p1p 2p2p 1p1p 1m1m 2m2m 2p2p 1p1p 2m2m 1p1p 2m2m 1p1p 2m2m 1m1m 2p2p 1m1m 2p2p 1m1m 2p2p Two equally probable arrangements: Independent assortment of nonhomologous chromosomes during meiosis

1 pair of homologous chromosomes gives 2 types of gametes (2 1 = 2) 2 pairs of homologous chromosomes gives 4 types of gametes (2 2 = 4) n pairs of homologous chromosomes gives 2 n types of gametes 23 pairs of homologous chromosomes gives 2 23 (8 million) types of gametes Examples: Meiosis and independent assortment of nonhomologous chromosomes can create many different 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 antigen = B antigen A red cells B red cells AB red cells O red cells

The ABO (I) gene There are 3 different versions (alleles) of the I gene: IBIB i IAIA A adds A sugar to red cell surface B adds B sugar to red cell surface adds no sugar to red cell surface I alleles

The ABO gene - dominance relationships I A is dominant to i The I gene lies on chromosome 9q34 I A /I A or I A /i - A blood type I B is dominant to iI B /I B or I B /i - B blood type I A is co-dominant with I B I A /I B - AB blood type i is recessivei/i - O blood type

Independent assortment of genes on nonhomologous chromosomes CFTR + CFTR - IAIA i CFTR + CFTR - IAIA i CFTR + IAIA CFTR - i IAIA CFTR + i IAIA IAIA CFTR - i i IAIA IAIA CFTR + i i Gametes formed from a CFTR +/- I A /i double heterozygote:

CFTR + IAIA CFTR - i IAIA CFTR + i IAIA CFTR - i Gametes that arise from a CFTR +/- I A /i double heterozygote: CFTR + i CFTR - IAIA 1/4

CFTR + I A CFTR + i CFTR - I A CFTR - i CFTR + I A CFTR - i CFTR + i CFTR - I A C +/+ I A /I A C +/- I A /i C +/+ I A /i C +/- I A /I A C +/- I A /i C +/+ I A /- C +/- I A /I A C -/- i/i C +/- i/i C -/- I A /i C +/- i/i C -/- I A /i C +/+ i/i C +/- I A /i C +/- I A /i C -/- I A /I A Eggs Sperm 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? Possible genotypes and phenotypes from a mating of CFTR +/- I A /i double heterozygotes

CFTR + I A CFTR + i CFTR - I A CFTR - i CFTR + I A CFTR - i CFTR + i CFTR - I A C +/+ I A /I A C +/- I A /i C +/+ I A /i C +/- I A /I A C +/- I A /i C +/+ I A /- C +/- I A /I A C -/- i/i C +/- i/i C -/- I A /i C +/- i/i C -/- I A /i C +/+ i/i C +/- I A /i C +/- I A /i C -/- I A /I A N, A 9 N, A N, O 3 N, O 3 CF, A 1 CF, O 1/4