1. Chapter 14: Human Inheritance
Section 14-2:
Human Genetic Disorders

2. From Molecule to Phenotype
There is a direct link between genotype and phenotype
Example:
People of African or European descent are more likely to have wet earwax (dominant) while those of Asian or Native American ancestry have the dry form (recessive)
The difference is in ONE BASE in the gene for a membrane-transport protein - a change from a G to an A
Changes in a gene’s DNA sequence can change proteins by altering their amino acid sequences, which may directly affect one’s phenotype

3. Disorders Caused by Individual Genes
Sickle Cell Disease
Caused by defective allele for beta-globin, part of hemoglobin
Makes hemoglobin less soluble, molecules stick together when blood’s oxygen level decreases
Molecules clump into long fibers, forcing cells into a sickle shape that are more rigid than normal RBCs, and they
Tend to get stuck in the capillaries
Can result in damage to cells, tissues, organs

4. Disorders Caused by Individual Genes
Cystic fibrosis (CF)
Most common among people of European ancestry
Most cases result from the deletion of just 3 bases in the gene for a protein called cystic fibrosis transmembrane conductance regulator (CFTR)
Amino acid phenylalanine is missing from the protein
CFTR normally allows chloride ions (Cl−) to pass across cell membranes - the removal of phenylalanine causes the protein to misfold, and it is destroyed

5. Disorders Caused by Individual Genes
CF con’t
Tissues malfunction because cell membranes can’t transport Cl-
Children with CF have serious digestive problems and produce thick, heavy mucus that clogs their lungs and breathing passageways
People with one normal copy of the CF allele are unaffected by CF, because they can produce enough CFTR to allow their cells to work properly
Two copies of the defective allele are needed to produce the disorder – it is recessive

7. Disorders Caused by Individual Genes
Huntington’s disease
Caused by a dominant allele for a protein found in brain cells
Allele contains a long string of bases in which the codon CAG (glutamine) repeats over and over again – more than 40X
Reason why is unknown
Symptoms of Huntington’s disease do not appear until middle age - mental deterioration and uncontrollable movements
The greater the number of codon repeats, the earlier the disease appears, and the more severe are its symptoms

8. Genetic Advantages
Why are alleles for sickle cell disease or CF still around if they can be fatal for those who carry them?
Individuals with one sickle cell allele are resistant to malaria
Individuals with one CF allele have a harder time developing typhoid fever

9. Chromosomal Disorders
Usually caused by nondisjunction
Creates gametes with an abnormal number of chromosomes

10. Chromosomal Disorders
If 2 copies of an autosome do not separate, a person can be born with 3 copies of that chromosome – known as trisomy
The most common form of trisomy is Down syndrome (trisomy 21)
Mild to severe mental retardation and a high frequency of certain birth defects

11. Chromosomal Disorders
Nondisjunction of X chromosomes can lead to Turner’s syndrome, where a woman only inherits one X chromosome
Called a monosomy
Sex organs do not develop properly at puberty, sterile, small/short stature, high voice
Karyotype: 45, XO

12. Chromosomal Disorders
Nondisjunction can also cause a male to inherit an extra X chromosome
Disorder called Klinefelter’s syndrome
Also sterile
Karyotype: 47, XXY