Human Genetic Disorders Autosomal Recessive Sickle-cell disease
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Transcript of Human Genetic Disorders Autosomal Recessive Sickle-cell disease
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