Human Genetic Disorders Autosomal Recessive Sickle-cell disease

1. Human Genetic Disorders • Autosomal Recessive • 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

3. Human Genetic Disorders • Autosomal Recessive • 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

4. Fig. 23.17

5. Malaria Sickle Cell Allele Frequency http://upload.wikimedia.org/wikipedia/commons/1/10/Malaria_versus_sickle-cell_trait_distributions.png

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

7. Human Genetic Disorders • Autosomal Recessive • 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

8. Human Genetic Disorders • Autosomal Dominant • 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 • 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

9. Chromosomal Theory of Inheritance • Proposed in early 1900s • Unified understanding of mitosis and meiosis with Mendel’s work on inheritance

10. Fig. 15.2

11. Linkage and Recombination • 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

12. Fig. 15.9

13. Linkage and Recombination • Recombination • Occurs during crossing over in meiosis • Drosophila example • F1 parent produced some recombinant gametes

14. Fig. 15.10

15. Linkage and Recombination • Recombination • Greater distance between genes  Greater probability of recombination • Distance between two genes expressed in map units • 1 map unit = 1% recombination frequency

16. Fig. 15.11