I. Human Genetic Disorders

A. Autosomal Recessive3. Sickle-cell disease

• Single amino acid substitution (valine for glutamate) in hemoglobin

• Causes some erythrocytes to form sickle shape• Abnormal erythrocytes slow blood flow and may block

capillaries

I. Human Genetic Disorders

A. Autosomal Recessive3. Sickle-cell disease

• Single amino acid substitution (valine for glutamate) in hemoglobin

• Causes some erythrocytes to form sickle shape• Abnormal erythrocytes slow blood flow and may block

capillaries• Most common in people of African descent (1 in 10

African Americans is heterozygous – “sickle cell trait”)• Why so common?

• May be advantageous in areas where malaria is a problem• Heterozygous people more resistant to malaria

than homozygous dominant people

Fig. 23.17

http://upload.wikimedia.org/wikipedia/commons/1/10/Malaria_versus_sickle-cell_trait_distributions.png

Malaria Sickle Cell Allele Frequency

http://www.cdc.gov/malaria/about/biology/sickle_cell.html

I. Human Genetic Disorders

A. Autosomal Recessive4. Tay-Sachs disease

• Absence in brain of enzyme that helps to break down membrane lipids and prevents their accumulation• Accumulation causes brain damage

• Especially common in people of Ashkenazi Jewish (Eastern European) descent• Possibly due to population bottleneck during

persecution & restriction to ghettos in Middle Ages

I. Human Genetic Disorders

B. Autosomal Dominant1. Achondroplasia

• Abnormal gene on chromosome 4 skeletal growth disorder dwarfism (relatively normal torso, short arms and legs)

• Most common growth-related disorder• Results from inheritance in <20% of cases

2. Huntington’s Disease• Defective allele proteins with long glutamine strands• Affects nervous system severe mental and physical

deterioration death• Typically appears later in life – Almost always before

age 50 but almost never before age 20• Usually after reproductive age

II. Chromosomal Theory of Inheritance

• Proposed in early 1900s• Unified understanding of mitosis and

meiosis with Mendel’s work on inheritance

Fig. 15.2

III. Linkage and Recombination

A. Linkage• Alleles don’t always assort independently

• Two genes on same homologous chromosome• Linkage first studied in Drosophila by

Thomas Morgan (early 1900s)• Worked with wild type and mutant fruit flies

• Studied inheritance with two-point test cross between heterozygous individual and homozygous recessive individual

Fig. 15.9

III. Linkage and Recombination

B. Recombination• Occurs during crossing over in meiosis• Drosophila example

• F1 parent produced some recombinant gametes

Fig.15.10

III. Linkage and Recombination

B. Recombination• Greater distance between genes

Greater probability of recombination• Distance between two genes expressed in

map units• 1 map unit = 1% recombination frequency

Fig. 15.11