Bio 178 Lecture 26Genetics

Reading

• Chapters 13 & 14

Quiz Material

• Questions on P 276-278 & 300

• Chapters 13 & 14 Quizzes on Text Website (www.mhhe.com/raven7)

Outline

• Genetics

Human Genetics (cntd)

Chromosomes and Genetics

• DNA

Experiments - DNA is hereditary material

Human Genetic Disorders

• Hemophilia

• Sickle Cell Anemia

• Huntington’s Disease

Dominantly Inherited Disorders - Huntington’s Disease

• The DiseaseDegenerative disease of the nervous system - progressive neural cell death caused by build up of the protein huntingtin (mutated form).

No cure. Terminal 10-30 years post-diagnosis.

• CauseAssociated with a triplet (CAG) repeat in the gene for huntingtin.

• GeneticsLethal in heterozygotes.

50% chance of passing the disease to progeny.

Huntington’s Disease (Cntd.)• Why does the allele persist?

Late onset of disease - symptoms at 35 to 40 years old.

http://www.thesahara.net/huntingtons_disease.htm

http://www.genephile.com.tw/Tests/huntington.htm

Basal Ganglia of HD Patient

http://www.stanford.edu/group/hopes/causes/neuro/d3.html

Caudate Nucleus

Chromosomal Theory of InheritanceWalter Sutton, 1902

• Pre-SuttonChromosomes, centrioles, and mitochondria all divide and segregate in meiosis.Which of these structures are responsible for heredity (follow Mendel’s rules)?

• Sutton’s Evidence (Sutton, 1877-1916)1. Gametes

(a) Must have equal hereditary contributions - sperm contain little cytoplasm, but do have nuclei. Hereditary material probably in the nucleus.

(b) Somatic cells have 2 homologous chromosomes, but gametes have only 1. Consistent with Mendel’s model.

Chromosomal Theory of Inheritance (Cntd.)• Sutton’s evidence (Cntd.)2. Mendel’s Laws

Chromosomes segregate and assort independently in meiosis.

• Response of the Scientific CommunityThere are more genes than chromosomes!

• The Final EvidenceThomas Hunt Morgan, 1910 - eye color in Drosophila.

Read P 265-266.

Morgan’s Experiment - Sex Linkage

Morgan’s Experiment - Sex Linkage (Cntd)

• Crossed the F1 females with the male parent.

• What ratio would you predict?

• Obtained a 1:1:1:1

Segregation of white eyed trait had a 1:1 correspondence with segregation of the X chromosome Mendel’s observation of segregation of alternate traits reflected chromosome behavior.

Autosomes and Sex Chromosomes• Autosomes

• Sex ChromosomesPrinciple function - sex determination.

• Which sex determines progeny sex (human)?

• Features of the Y Chromosome (human)Carries 78 active genes, including a sex-determining gene (SRY).

• Sex Linked Genes

Any gene (does not have to be involved with sex) that is carried on the sex chromosomes (usually on X).

Sex Determination in Different Organisms

Barr Body 1 X chromosome in each female somatic cell is inactivated early in development female cells produce the same amount of protein from the X as do male cells.

http://www.carolguze.com/text/442-4-chromosome_abnormalities.shtml

NondisjunctionThe failure of homologues or sister chromatids to separate in meiosis aneuploidy.

• Nondisjunction of Autosomes

Effects are either fatal or severe.

Down Syndrome (Trisomy 21)

Nondisjunction (Cntd.)• Nondisjunction of Sex Chromosomes

Generally, the effects are not as severe as nondisjunction of autosomes.

1. X Chromosome

(a) Triple X Syndrome

Usually taller than average females, generally “normal” and most are *fertile.

(b) Klinefelter Syndrome

XX + Y XXY

Sterile male with female characteristics and sometimes mildly impaired intelligence.

Klinefelter Syndrome

http://www.carolguze.com/text/442-4-chromosome_abnormalities.shtml

Klinefelter calico cat - evidence that Y chromosome determines maleness.

Nondisjunction of Sex Chromosomes (Cntd.)

(c) Turner Syndrome (Monosomy X)

X + O XO

Short females with edema (resulting in webbed neck) that are almost always sterile.

http://www.carolguze.com/text/442-4-chromosome_abnormalities.shtml

Nondisjunction of Sex Chromosomes (Cntd.)

(d) OY

O (egg) + Y OY

Lethal - genes on the X chromosome are necessary for survival.

2. Y Chromosome

X + YY (sperm) XYY

Tall, fertile males.

Genetic Counseling

Read P 274.

Nondisjunction

Nondisjunction

Abnormality

F Meiosis I

F Meiosis II

M Meiosis I

M Meiosis II

Trisomies 75-95% 5-25% 0

45, X 20% 80%

3N ~25% 0-25%

4N

Nondisjunction

Chromosome AbnormalitySpontaneous Abortion (%)

All 50

Trisomy 16 7.5

Trisomy 13, 18, 21 4.5

XXX, XXY, XYY 0.3

All other trisomies 13.8

45, X 8.7

3N 6.4

4N 2.4

Structural Abnormalities 2.0

Pedigree Example

The above pedigree is for a rare kidney disease. Deduce the inheritance (autosomal, sex-linked, dominant, recessive).