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

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

Snapdragons – Incomplete Dominance

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

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

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

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?

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

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

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)

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

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

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

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

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

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

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

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

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

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