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.

• Parents are two true-breeding pea plants

• Parent 1 Yellow, round Seeds (YYRR)

• Parent 2 Green, wrinkled seeds (yyrr)

These 2 genes are on different chromosomes.

Draw meiosis to determine the resulting gametes of parent 1.

How do the resulting gametes connect to Punnett squares?

• F1: YyRr x YyRr

• What are the predicted phenotypic ratios of the offspring?

• ¾ yellow ¾ round

• ¼ green ¼ wrinkled

¼ (green) x ¼ (wrinkled) = 1/16 green, wrinkled

9:3:3:1 phenotypic ratio

First Experimental Evidence to connect Mendelism to the chromosome

• Thomas Morgan (1910)

• 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

• 3 pairs of Autosomes• 1 pair of sex chromosomes

Examples

• Wild type is most common, NOT dominant or recessive• 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.

• Male ww x Female w+w+

The F1 offspring:

• All had red eyes.

• This suggests that white eyes is a _________?

• Recessive.

• F1= w+w

• What is the predicted phenotypic ratio for the F2 generation?

F1 X F1 = F2

• Expected F2 ratio - 3:1 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 gene are located on the sex chromosome

Fruit Fly Chromosomes

• Female Male• XX XY

• Presence of Y chromosome determines the sex

• Just like in humans!

Morgan Discovered

• There are many genes, but only a few chromosomes.

• Therefore, each chromosome must carry a number of genes together as a “package”.

Sex-Linked Problem• A man with hemophilia (a recessive, sex-

linked, x-chromosome condition) has a daughter of normal phenotype. She marries a man who is normal for the trait.

• A. What is the probability that a daughter of this mating will be a hemophiliac?

• B. That a son will be a hemophiliac? • C. If the couple has four sons, what is the probability that

all four will be born with hemophilia?

• Original Man - XhY • Daughter - must get the dad’s X chromosome XHXh

(normal phenotype, so she’s a carrier)• Daughter’s husband XHY (normal phenotype)

• A. daughter must get XH from the dad. 0% (50% carrier, 50% homo dom.)

• B. son must get Y from dad. 50% chance to be hemophiliac

• C. ½ x ½ x ½ x ½ = 1/16

Linked Genes• Traits that are located on the same

chromosome.• Result:

• Failure of Mendel's Law of Independent Assortment.

• Ratios are different from the expected

Example:• Body Color - gray dominant

• b+ - Gray • b - black

• Wing Type - normal dominant• vg+ - normal • vg – vestigial (short)

Example

b+b vg+vg X bb vgvg

Predict the phenotypic ratio of the offspring

Show at board

b+b x bb vg+vg x vgvg

½ gray ½ black ½ normal ½ vestigial

-----------------------------------------------------¼ gray normal, ¼ gray vestigial,

¼ black normal, ¼ black vestigial

1:1:1:1 phenotypic ratio

Conclusion• Most offspring had the parental phenotype.

Both genes are on the same chromosome.

• What do you expect to happen if they’re on the same chromosome? (draw chromosomes)

• bbvgvg parent can only pass on b vg

• b+b vg+vg can pass on b+ vg+ or b vg

b+b vg+vg - Chromosomes (linked genes)

Crossing-Over

• Breaks up linkages and creates new ones.

• Recombinant offspring formed that doesn't match the parental types.

• Higher recombinant frequency = genes further apart on chromosome

If Genes are Linked:

• Independent Assortment of traits fails.

• Linkage may be “strong” or “weak”.

• Strong Linkage means that 2 alleles are often inherited together.

• Degree of strength related to how close the traits are on the chromosome.

Genetic Maps• Constructed from crossing-over

frequencies.

• 1 map unit = 1% recombination frequency.

• Can use recombination rates to ‘map’ chromosomes.

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

• Over 50% gives the same phenotypic ratios as genes on separate chromosomes

Genetic Maps

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

Sex Linkage in Biology• Several systems are known:1. Mammals – XY and XX2. Diploid insects – X and XX3. Birds – ZZ and ZW4. 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 - XYFemales - 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 CH3 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: 2N - 1

• Trisomy: 2N + 1

Turner Syndrome

• 2N - 1 or 45 chromosomesGenotype: X_ or X0.

• 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.

Homework

• Read Chapter 15 (Hillis – 8)

• Genetics Lab Report – today

• No class Feb. 4 and 5

• Chapter 15 – Thurs. 2/7

Other Sex Chromosome changes

• Kleinfelter Syndrome

• Meta female

• Supermale

Kleinfelter Syndrome• 2N + 1

• Genotype: XXY

• Phenotype: male, but sexual development may be poor. Often taller than average, mental development fine, usually sterile.

Meta female

• 2N + 1 or 2N + 2

• Genotype: XXX or XXXX

• Phenotype: female, but sexual development poor. Mental impairment common.

Super male

• 2N + 1 or 2N + 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= 3N

• Tetraploid= 4N

• 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.

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 African Violets

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.