Extensions of Mendelian Genetics

1. Extensions of Mendelian Genetics • Mendelian genetics seems to be relevant to only a small set of heritable features • For only a few characters there are… • Only 2 versions of an allele (green or yellow) • 1 gene codes for a single external character • 1 allele is completely dominant to the other • The basic patterns of segregation & independent assortment apply to more complex patterns of inheritance

2. Different Types of Dominance • Complete dominance • Phenotype of heterozygote & HomoD are indistinguishable • The pattern with which you are already familiar • Incomplete dominance • Phenotype of heterozygote is in between the 2 Homo phenotypes • Example: pink snapdragons

3. Snapdragons – Incomplete Dominance

4. So incomplete dominance does NOT provide evidence for “blending” theories

5. Codominance • Codominance • Phenotype of heterozygote is separate & distinguishable from Homozygous Dominant & Homozygous Recessive • Example: AB blood type or Rhododendron flower

6. Dominance & Phenotype • The observed dominance/recessiveness of alleles depends on the level of the investigation • Consider Tay-Sachs disease • Brain cells of the baby do not metabolize certain lipids • As lipids accumulate, seizures, blindness, and mental degeneration • Death occurs within a few years of conception

7. Tay-Sachs Disease • At the Organismal level, the disease is recessive • Only children with 2 copies of the recessive trait will have the malady • Heterozygote is not afflicted – they produce some lipid-metabolizing enzyme, though not as much as in HomoD • So intermediate enzyme production • This suggests that @ the biochemical level, the disease is an example of incomplete dominance • Which is Tay-Sachs: dominance or incomplete dominance?

8. Prevalence & Dominance • Polydactyly • Extra fingers or toes • 1 of 400 in the US • The allele for polydactyly is dominant, but rarely present • Recessive homozygotes (HomoR) are found 399 out of 400 instances

9. Blood Typing • Only 2 alleles existed for Mendel’s peas, but this is not typical for most traits • Consider ABO blood group in humans • A refers to the “A” membrane carbohydrate & type A blood • B refers to (seriously, I’m not writing this down) • O means neither A or B carbohydrate is found • AB means both A & B are found • BUT the A and B alleles are codominant and are both expressed if an individual inherits both alleles

11. Epistasis • A gene at one locus alters the phenotypic expression of a gene at a second locus • Example: Mouse fur color • Bb or BB = Black bb = brown • If HomoR for (C) gene [cc], then no fur color (albino or white) • Regardless of fur color specified by brown-black gene • If NOT HomoR for (c) gene [Cc or CC], then can be brown (bb) or black (Bb or BB)

12. What is the phenotype of… • BBcc? • BbCc? • bbCC? • Bbcc? • BBCC? • bbcc?

13. Pleiotrophy • Single gene has multiple effects • Should be unsurprising given intricate molecular and cellular interactions for development of an organism • Phenylketonuria • Mental Retardation • Reduced skin and hair pigmentation

14. Polygenic Inheritance • The additive effect of 2 or more genes on 1 phenotypic character • Called quantitative characters since there is a continuum of gradations • Normal curve of phenotypes • Example: human skin pigmentation is determined by at least 3 separately inherited genes • AABBCC = Dark • AaBbCc = Intermediate • aabbcc = Light

16. Pedigree Analysis • Family tree describing the interrelationships of parents & children across the generations

17. Recessively Inherited Disease • Requires 2 copies of the recessive allele (Homozygous Recessive) to express the mality • Heterozygotes are called carriers • Normal phenotype, but may transmit disease to offspring • Examples: • Cystic Fibrosis • Tay Sachs disease • Sickle-cell disease

18. Cystic Fibrosis • Recessive autosomal disease • Common in those of European descent • 1 of 2,500 affected, but 1 of 25 are carriers • Affects Chloride ion transport between a cell and extracellular fluid • If untreated, most die before 5th birthday • Typically, patients live until their 20s or 30s with efficacious treatment

19. Sickle-Cell Anemia • Recessive autosomal disease • African descent • Affects Hemoglobin protein in RBCs • Low blood oxygen = hemoglobin molecules clump together forming sickle shaped RBCs • Sickle-celled RBCs clump together creating chronic vascular occlusion of small vessels • Example of incomplete dominance • Heterozygotes are usually normal but will show some symptoms during prolonged periods of reduced blood oxygenation

20. Dominant Alleles • Most harmful alleles are recessive, but some human diseases are due to dominant alleles • Only require one copy of the allele to be expressed • Hypothesis: if there is a lethal disease carried on a dominant allele, it would have burned out its carriers by now. • UNLESS, the lethal disease carried by a dominant allele is one that affects organisms of advanced age • Like Huntington’s disease

21. Examples of Dominant Allele Disease • Achondroplasia – form of dwarfism • Heterozygous individual = dwarf • 1 in 25,000 have achondroplasia, so 99% of the population are HomoR • Huntington’s disease • Caused by a lethal dominant allele • Degenerative disease of nervous system • Usually only affects those > 40 yrs old

22. Genetic Testing • Pedigree analysis gives some info about risk to offspring • There are also tests to identify carriers of certain genetic diseases • Amniocentesis – amniotic fluid is removed and then cells contained in the fluid are cultured to identify certain chromosomal defects via karyotype • Chorionic villus sampling (CVS) – placental tissue is removed for same purpose as amnio, but results are available far faster, & can be performed earlier in pregnancy • Karyotype can be immediately obtained