Genes and Medical Genetics

1. Genes and Medical Genetics Chapter 2

2. Genotype = all the genes that an individual has Phenotype = physical appearance of the individual Genotype and Phenotype Pictures of Jennifer Aniston

3. Genotype (con’t) • Alleles can be dominant (capital letter) or recessive (lower case letter). • Alternate forms of a gene having the same position (locus) on a pair of matching chromosomes that control the same trait are called alleles • An individual has two alleles for each trait because a chromosome pair carries alleles for the same traits • How many alleles for each trait will be in the gametes?

4. Example – in humans unattached earlobe is dominant over attached earlobes • Could use capital E to show dominant allele and lower case e to show recessive (non-dominant) allele Note: it is customary to designate alleles by the same letter, with uppercase to signify dominant and lowercase to signify recessive Fig. 02-01

5. When the two alleles are both dominant it is called a homozygous dominant genotype • The phenotype will be unattached earlobes • When the two alleles are both recessive it is called homozygous recessive • The phenotype will be attached earlobes • When the two alleles are different (one dominant, one recessive) it is called a heterozygous genotype • The phenotype will be ________________. Fig. 02-01

6. Forming gametes (gametogenesis) (Chromosomes already doubled) • Recall: gametes have ½ normal # of chromosomes • Happens when chromosome pair separates during meiosis • Since alleles are on chromosomes, they also separate during meiosis, thus gametes only carry one allele for each trait. • Ex. If individual was Ee, and produced four gametes, ½ would be E and ½ would be e. Fig. 02-02 Gametogenesis

7. Fig. 02-03 Common Inherited Character -istics in Humans Phenotypes Genotypes WW or Ww ww EE or Ee ee SS or Ss ss FF or Ff ff

8. Genetic Crosses(One-trait Crosses) • If know genotype of parents, can predict chances of having a child with certain genotypes (and thus certain phenotypes). • Ex. If one parent is homozygous dominant (EE) the chance of having a child with unattached earlobes is 100% because parent only has dominant allele (E) to pass on to baby. • But, if both parents are homozygous recessive (ee), the chance of having a child with attached earlobes is 100% because parents only have recessive allele (e) to pass on to baby.

9. Fig. 02-04 Heterozygous-by- Heterozygous cross One-trait Crosses (con’t) • If both parents are heterozygous (Dad is Ee, and Mom is Ee), what are the chances that baby will have unattached or attached earlobes? • Determine using a Punnett Square • Each child will have a 75% chance of dominant phenotype (unattached), and 25% chance of having recessive phenotype (attached). Punnett Square

10. Fig. 02-05 Heterozygous By Homozygous cross One-trait crosses (con’t) • What if one parent is Ee and the other is ee? • Each child will have a 50% chance of having unattached earlobes Punnett Square

11. Genetic Crosses(Two-trait Crosses) • What if want to look at two traits at the same time? • Ex. Widow’s peak (W) and short fingers (S) (both dominant traits). • If one parent is homozygous for widow’s peak and short fingers (WWSS) and other is homozygous for straight hairline and long fingers (wwss), what will • Children look like? • Grandchildren look like?

12. Fig. 02-06 Dihybrid cross using Punnett Square • Expected phenotypic ratio for a dyhibrid cross is always 9:3:3:1 • Can use this expected ratio to predict chances of each child receiving a certain phenotype • Ex. Chance of getting two dominant phenotypes together is 9 out of 16 • Chance of getting two recessive phenotypes is 1 out of 16

13. Autosomal Dominant Disorders • Genetic disorders are caused by mutations • Mutations – permanent changes in genes (DNA) • If disorder is autosomal dominant  mutation is a single allele, and heterozygotes will exhibit the disorder • If know genotype of parents, can determine chances of children having the disorder (see Table 2.2, p. 26) • Can provide genetic counseling to parents who can make decision about best courses of action (Chapter 4).

14. Autosomal Dominant Disorders • Neurofibromatosis • Most common genetic disorders (1 in 3,500 newborns, all races and ethnicities) • Symptoms • Large tan spots on skin that get darker with age • Small, benign (?) tumors (neurofibromas) often occur in nerves • If severe case • Skeletal deformities (including a large head) • May develop eye and ear tumors  become blind and deaf • Children with non-severe symptoms may still have learning disabilities and be hyperactive • Gene for neurofibromatosis has been located on chromosome 17 • Found that gene controls production of protein that usually blocks cell growth • If gene not working  certain cells grow out of control =_______________ .

15. Autosomal Dominant Disorders • Huntington Disease • Neurological (nervous system) disorder that causes progressive degeneration of brain cells. • Symptoms • Most patients appear normal until middle age (may already have children) • Severe muscle spasms • Personality disorders • Treatment – none (patients die in 10 – 15 years after symptoms appear) • Gene (mutated) located on chromosome 4  causes abnormal protein that clumps inside neurons (nerve cells) • Test developed for presence but most people do not want to know • Two minute paper: “Would you want to be tested for a fatal genetic disease? Why or why not?”

16. Autosomal Recessive Disorders • Cystic Fibrosis (CF) • Most common lethal genetic disease among Caucasians in the US • 1 in 20 are a carrier, 1 in 2,500 newborns has it • Caused by defect in plasma membrane (gene on chromosome 7) • Symptoms • Thickened mucous in bronchial tubes (problems breathing) and pancreatic duct (problems digesting) • Treatment – mucous in lungs manually loosened and other treatments have raised life expectancy to 35-40 years old

17. Fig. 02-08 Treatment for CF

18. Autosomal Recessive Disorders • Phenylketonuria (PKU) • Not so common as CF • Affects nervous system development • Caused by missing enzyme that normally allows metabolism of the amino acid phenylalanine • Causes abnormal breakdown product (phenylketone) in urine • Symptoms – severe mental retardation, black urine • PKU allele located on chromosome 12  prenatal DNA test can detect it (and elevated phenylalanine in blood) • If detect  place newborn on diet low in phenylalanine until at least age 7

19. Autosomal Recessive Disorders • Tay-Sachs Disease • Usually occurs in Jewish people • Symptoms • Development slows at age 4 to 8 months • Neurological and Psychomotor impairment • Child gradually becomes blind and helpless, seizures, paralyzed, death by age 3 – 4 years old • Caused by gene on chromosome 15  caused buildup of nonfunctional lysosomes in neurons

20. Autosomal Recessive Disorders • Albinism • Person unable to produce pigment melanin  colors skin, hair, eyes • Symptoms • White hair, pink eyes, super-white skin • Vision problems • Example of epistasis  one gene affects the expression of other genes • In albino  any gene for coloring cannot be expressed because mutated gene prevents them from producing melanin • Picture of Johnny Winter