Chapter 15 The Chromosomal Basis of Inheritance

Timeline • • 1866 - Mendel's Paper 1875 - Mitosis worked out 1890's- Meiosis worked out 1902 - Sutton, Boveri et. al. connect chromosomes to Meiosis.

Sutton • Developed the “Chromosome Theory of Inheritance”. • Mendelian factors or alleles are located on chromosomes. • Chromosomes segregate and show independent assortment.

Morgan • Chose to use fruit flies as a test organism in genetics. • Allowed the first tracing of traits to specific chromosomes.

Fruit Fly • Drosophila melanogaster • Early test organism for genetic studies.

Reasons • • • Small Cheap to house and feed Short generation time Many offspring Few chromosomes

Genetic Symbols • Mendel - use of uppercase or lowercase letters. T = tall t = short • Morgan: symbol from the mutant phenotype. + = wild phenotype

Examples • Recessive mutation: • w = white eyes • w+ = red eyes • Dominant Mutation • Cy = Curly wings • Cy+ = Normal wings

Morgan Observed: • A male fly with a mutation for white eyes.

Morgan crossed • The white eye male with a normal red eye female.

The F 1 offspring: • All had red eyes. • This suggests that white eyes is a genetic _____? • Recessive.

F 1 X F 1 = F 2 • Morgan expected the F 2 to have a 3: 1 ratio of red: white • He got this ratio, however, all of the white eyed flies were MALE. • Therefore, the eye color trait appeared to be linked to sex.

Morgan discovered: • Sex linked traits. • Genetic traits whose expression are dependent on the sex of the individual.

Fruit Fly Chromosomes

Sex linked traits • Sex linked traits in humans will be covered in a few minutes.

Morgan Discovered • There are many genes, but only a few chromosomes. • Therefore, each chromosome must carry a number of genes together as a “package”.

Linked Genes • Traits that are located on the same chromosome. • Result: • Failure of Mendel's Law of Independent Assortment. • Ratios mimic monohybrid crosses.

Body Color and Wing type

Example b+b vg+vg X bb vgvg (b+ linked to vg+) (b linked to vg) If unlinked: 1: 1 ratio. If linked: ratio will be altered.

Crossing-Over • Breaks up linkages and creates new ones. • Recombinant offspring formed that doesn't match the parental types.

If Genes are Linked: • Independent Assortment of traits fails. • Linkage may be “strong” or “weak”.

Linkage Strength • Degree of strength related to how close the traits are on the chromosome. • Weak - farther apart • Strong - closer together

Genetic Maps • Constructed from crossing-over frequencies. • 1 map unit = 1% recombination frequency.

• Comment - only good for genes that are within 50 map units of each other. Why?

Genetic Maps • Have been constructed for many traits in fruit flies, humans and other organisms.

Sex Linkage in Biology • 1. 2. 3. 4. Several systems are known: Mammals – XY and XX Diploid insects – X and XX Birds – ZZ and ZW Social insects – haploid and diploid

Chromosomal Basis of Sex in Humans • X chromosome - medium sized chromosome with a large number of traits. • Y chromosome - much smaller chromosome with only a few traits.

Human Chromosome Sex • Males - XY Females - XX • Comment - The X and Y chromosomes are a homologous pair, but only for a small region at one tip.

SRY • Sex-determining Region Y chromosome gene. • If present - male • If absent - female • SRY codes for a cell receptor.

Sex Linkage • Inheritance of traits on the sex chromosomes. • X- Linkage (common) • Y- Linkage (very rare if exists at all)

Males • Hemizygous - 1 copy of X chromosome. • Show ALL X traits (dominant or recessive). • More likely to show X recessive gene problems than females.

X-linked Disorders • • Color blindness Duchenne's Muscular Dystrophy Hemophilia (types a and b) Immune system defects

Samples of X-linked patterns:

X-linked Patterns • Trait is usually passed from a carrier mother to 1/2 of sons. • Affected father has no affected children, but passes the trait on to all daughters who will be carriers for the trait.

Comment • Watch how questions with sex linkage are phrased: • Chance of children? • Chance of males?

Can Females be color-blind? • Yes, if their mother was a carrier and their father is affected.

Y-linkage • Hairy ear pinnae. • Comment - new techniques have found a number of Y-linked markers that can be shown to run in the males of a family. • Ex: Jewish priests

Sex Limited Traits • Traits that are only expressed in one sex. • Ex – prostate

Sex Influenced Traits • Traits whose expression differs because of the hormones of the sex. • These are NOT on the sex chromosomes. • Ex. – beards, mammary gland development, baldness

Baldness • Testosterone – the trait act as a dominant. • No testosterone – the trait act as a recessive. • Males – have gene = bald • Females – must be homozygous to have thin hair.

Barr Body • Inactive X chromosome observed in the nucleus. • Way of determining genetic sex without doing a karyotype.

Lyon Hypothesis • Which X inactivated is random. • Inactivation happens early in embryo development by adding CH 3 groups to the DNA. • Result - body cells are a mosaic of X types.

Examples • Calico Cats. • Human examples are known such as a sweat gland disorder.

Calico Cats • XB = black fur • XO = orange fur • Calico is heterozygous, XB XO.

Question? • Why don’t you find many calico males? • They must be XB XOY and are sterile.

Chromosomal Alterations • Changes in number. • Changes in structure.

Number Alterations • Aneuploidy - too many or too few chromosomes, but not a whole “set” change. • Polyploidy - changes in whole “sets” of chromosomes.

Nondisjunction • When chromosomes fail to separate during meiosis • Result – cells have too many or too few chromosomes which is known as aneuploidy

Meiosis I vs Meiosis II • Meiosis I – all 4 cells are abnormal • Meiosis II – only 2 cells are abnormal

Aneuploidy • Caused by nondisjunction, the failure of a pair of chromosomes to separate during meiosis.

Types • Monosomy: 2 N - 1 • Trisomy: 2 N + 1

Turner Syndrome • 2 N - 1 or 45 chromosomes Genotype: X_ or X 0. • Phenotype: female, but very poor secondary sexual development.

Characteristics • • • Short stature. Extra skin on neck. Broad chest. Usually sterile Normal mental development except for some spatial problems.

Question • Why are Turner Individuals usually sterile? • Odd chromosome number. • Two X chromosomes need for ovary development.

Other Sex Chromosome changes • Kleinfelter Syndrome • Meta female • Supermale

Kleinfelter Syndrome • 2 N + 1 • Genotype: XXY • Phenotype: male, but sexual development may be poor. Often taller than average, mental development fine, usually sterile.

Meta female • 2 N + 1 or 2 N + 2 • Genotype: XXX or XXXX • Phenotype: female, but sexual development poor. Mental impairment common.

Super male • 2 N + 1 or 2 N + 2 • Genotype: XYY or XYYY • Phenotype: male, usually normal, fertile.

Trisomy events • Trisomy 21: Down's Syndrome • Trisomy 13: Patau Syndrome • Both have various physical and mental changes.

Question? • Why is trisomy more common than monosomy? • Fetus can survive an extra copy of a chromosome, but being hemizygous is usually fatal.

Question? • Why is trisomy 21 more common in older mothers? • Maternal age increases risk of nondisjunction.

Polyploid • Triploid= 3 N • Tetraploid= 4 N • Usually fatal in animals.

Question? • In plants, even # polyploids are often fertile, why odd # polyploids are sterile. Why? • Odd number of chromosomes can’t be split during meiosis to make spores.

Structure Alterations • • Deletions Duplications Inversions Translocations

Translocations

Result • Loss of genetic information. • Position effects: a gene's expression is influenced by its location to other genes.

Cri Du Chat Syndrome • Part of p arm of #5 missing. • Good survival, but low birth weight and slow gain. • Severe mental impairment. • Small sized heads common.

Cri Du Chat Syndrome

Philadelphia Chromosome • An abnormal chromosome produced by an exchange of portions of chromosomes 9 and 22. • Causes chronic myeloid leukemia.

Assignments • Read Chapter 15, Chapter 8 in Hillis • Lab – Genetics of Organisms – see Black. Board for write-up directions. Due today • Chapter 15 – due Friday. • Exam 1 – next week (Tuesday)

Parental Imprinting of Genes • Gene expression and inheritance depends on which parent passed on the gene. • Usually caused by different methylations of the DNA.

Example: • Prader-Willi Syndrome and Angelman Syndrome • Both lack a small gene region from chromosome 15. • Male imprint: Prader-Willi Female imprint: Angelman

Cause: • Imprints are "erased" in gamete producing cells and re-coded by the body according to its sex. • Gametes are methylated to code as “male “ or “female”.

Result • Phenotypes don't follow Mendelian Inheritance patterns because the sex of the parent does matter.

Extranuclear Inheritance • Inheritance of genes not located on the nuclear DNA. • DNA in organelles. • Mitochondria • Chloroplasts

Result • Mendelian inheritance patterns fail. • Maternal Inheritance of traits where the trait is passed directly through the egg to the offspring.

Chloroplasts • Gives non-green areas in leaves, called variegation. • Several different types known. • Very common in ornamental plants.

Variegation in Violets African

Variegated Examples

Mitochondria • • Myoclonic Epilepsy Ragged Red-fiber Disease Leber’s Optic Neuropathy All are associated with ATP generation problems and affect organs with high ATP demands.

Comment • Cells can have a mixture of normal and abnormal organelles. • Result - degree of expression of the maternal inherited trait can vary widely.

Summary • Know about linkage and crossing-over. • Sex chromosomes and their pattern of inheritance.

Summary • Be able to work genetics problems for this chapter.