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 F1 offspring:

• All had red eyes.

• This suggests that white eyes is a genetic _________?

• Recessive.

F1 X F1 = F2

• Morgan expected the F2 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

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: 1:1:1:1 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

• Several systems are known:

1. Mammals – XY and XX

2. Diploid insects – X and XX

3. Birds – ZZ and ZW

4. 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 surface 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 acts as a dominant.

• No testosterone – the trait acts 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 methyl (CH3) groups to the DNA.

• Result - body cells are a mosaic of X types.

X Inactivation 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 chromosomes Genotype: 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.

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.

Chromosome Structure Alterations

• Deletions

• Duplications

• Inversions

• Translocations

Translocations

Results of Translocation

• 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 chromosome 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.

• Be able to work genetics problems for this chapter.