1. Ch 15 Genetics Part II Non-mendelian Inheritance and Chromosomal Abnormalities

2. When a heritable phenotype is NOT controlled by one gene with two alleles, only Non-Mendelian Inheritance Examples? 1. When alleles are not completely dominant or recessive Incomplete dominance Codominance 3. When a gene produces multiple phenotypes Pleiotropic 2.When a gene has more than two alleles Multiple alleles

3. The Spectrum of Dominance Complete dominance: - when heterozygous and dominant homozygous phenotypes are identical Incomplete dominance: - phenotype of F 1 hybrids is between phenotypes of parental varieties Codominance: - when two dominant alleles affect the phenotype in separate, distinguishable ways

4. LE 14-10 Red C R Gametes P Generation CRCR CWCW White C W Pink C R C W CRCR Gametes CWCW F 1 Generation F 2 Generation Eggs CRCR CWCW CRCR CRCRCRCR CRCWCRCW CRCWCRCW CWCWCWCW CWCW Sperm 1 2 1 2 1 2 1 2 1 2 1 2 Incomplete dominance Carry out an F1 cross an a Punnett square.

5. What causes these phenotypes? C gene: encodes an enzyme that catalyzes the formation of red pigment C R allele: normal activity C W allele: mutant gene that encodes non-functional enzyme Explain red, white and pink

6. Example of both: and Multiple alleles and codominance codominance

7. Explanation of blood cell type I gene: encodes enzyme that adds certain carbohydrates to the exterior surface of RBCs I A : adds “A” carbohydrates I B : adds “B” carbohydrates I O : defective enzyme; no carbohydrates added

8. Pleiotropy When one gene has multiple phenotypic effects For example, pleiotropic alleles are responsible for the multiple symptoms of certain hereditary diseases, such as sickle-cell disease What are symptoms (phenotypes) of sickle-cell disease?

9. Epistasis When a gene at one locus alters the phenotypic expression of a gene at a second locus

10. LE 14-11 Sperm BC bCBc bc BbCcBBCcBbCCBBCC BbCC bbCCBbCc bbCc BbccBBcc BbCcBBCc BbCc bbCc Bbcc bbcc BC bC Bc bc BbCc 1 4 1 4 1 4 1 4 1 4 1 4 1 4 1 4 9 16 3 4 B=black b=brown C=pigment deposition c=no pigment deposition Epistasis C/c is epistatic to B/b.

11. Polygenic Inheritance When two or more genes affect a single phenotype Examples Often quantitative traits such as height and skin color Trait varies in a bell shape curve in a population

12. LE 14-12 aabbccAabbccAaBbccAaBbCcAABbCcAABBCcAABBCC AaBbCc 20 / 64 15 / 64 6 / 64 1 / 64 Fraction of progeny Polygenic effect What correlation exists between the alleles and skin color? More dominant alleles Darker skin Additive effect Increasing skin darkness

13. Environmental Impact Phenotype is influenced by environmental factors. For example, what environmental factors influence skin color Norm of reaction the range of phenotypes from a genotype in any given environment. Nature and Nurture

14. Hydrangea: a flowering woody shrub Grown in acidic soil Grown in alkaline soil

15. Multifactorial effects influenced by many genes and environmental factors What diseases might be considered multifactorial? Heart disease, high blood pressure, diabetes, cancer

16. Human traits: determining mode of inheritance and frequency Disadvantages as genetic model system Unethical as an experimental model system Slow generation time Low numbers of offspring Advantages Oral and written histories, medical records Ability to construct retrospective pedigrees Abiltiy to predict future probability of inheritance

17. LE 14-14a Wwww Ww wwWwww Ww WWww or Ww No widow’s peak Third generation (two sisters) Widow’s peak Second generation (parents plus aunts and uncles) First generation (grandparents) Dominant trait (widow’s peak) (WW or Ww)(ww)

18. Pedigree Problems Female Male

19. LE 14-14b First generation (grandparents) Second generation (parents plus aunts and uncles) Third generation (two sisters) Attached earlobe Free earlobe Recessive trait (attached earlobe)

20. LE 14-14b First generation (grandparents) Ff FF or Ffff Ff ff Ff Second generation (parents plus aunts and uncles) Third generation (two sisters) Attached earlobe Free earlobe ffFF or Ff Recessive trait (attached earlobe)

21. Recessive Autosomal Inherited Disorders Detectable in individuals homozygous for the allele Heterozygous individuals are phenotypically normal; carry one recessive allele; called carriers Example: Cystic Fibrosis

22. Cystic Fibrosis Frequency –One out of every 2,500 people of European descent Most frequent genetic disease in US (carrier frequency 1 in 20) Mutation in cystic fibrosis allele - gene encodes CF transmembrane transporter –Causes defective or absent chloride transport channels in plasma membranes--> high Na+ & Cl- excretion Symptoms –Mucus buildup in some internal organs –abnormal absorption of nutrients in the small intestine – prone to infections – lethal Do some crosses

23. Most defective alleles are recessive. Why? Is there a practical reason? If defective dominant allele: - Immediate decrease in fitness -Individuals who have the defective dominant allele likely won’t survive or pass on this allele. Recessive alleles Favored No detrimental effect in heterozygous state

24. Individuals homozygous for the recessive mutant CF allele tend to die before childbearing age. What effect will that have on the frequency of the mutant allele in the population? Should go down because it reduces fitness(ability to reproduce) and eventually disappear. Why is the mutant CF still so prevalent? Hypothesis: correlates with distribution of tuberculosis. CF carriers may have been more resistant to TB infection due to elevated of levels of lung mucous.

25. Mating of Close Relatives Consanguineous matings (Inbreeding) Increased likelihood of genetic disorders Why? Higher probability of two recessive alleles occurring in homozygous state Laws forbid marriage between first cousins or closer.

26. Dominant-Autosomal Inherited Disorders Achondroplasia –Form of dwarfism, arrested growth of long bones –Dominant –Lethal when homozygous

27. Huntington’s disease (dominant autosomal) –Degenerative disease of the nervous system –No obvious phenotypic effects until about 35 to 40 years of age Implications: not selected against phenotype appears after child bearing years allele remains in population Genetic Counseling & Screening: Under what circumstances might it be of value to undergo genetic testing?

29. Abnormal Chromosome Number Can produce distinctive phenotype Mechanism Meiotic Nondisjunction: –Tetrads or chromatid sisters fail to separate during anaphase I or II

30. LE 15-12 Meiosis I Nondisjunction Meiosis II Nondisjunction Gametes n + 1 Number of chromosomes Nondisjunction of homologous chromosomes in meiosis I n + 1n – 1 n + 1n – 1nn Nondisjunction of sister chromatids in meiosis I

31. Abnormal Chromosome Number Result of Nondisjunction Aneuploidy - Some gametes receives too many chromosomes - Others not enough - At fertilization, zygote has abnormal chromosome number

32. Analyze karyotype Sex? Other?

33. Down Syndrome Aneuploid condition --> three copies of chromosome 21 One out of every 700 children born in US Frequency of Down syndrome increases with mother’s age

34. Trisomic zygote: –three copies of a particular chromosome Monosomic zygote: –one copy of a particular chromosome Polyploidy –condition in which an organism has more than two complete sets of chromosomes

35. Polyploid rodent: tetraploid T. barrerae

36. LE 15-14 Deletion Duplication Inversion Reciprocal translocation A deletion removes a chromosomal segment. A duplication repeats a segment. An inversion reverses a segment within a chromosome. A translocation moves a segment from one chromosome to another, nonhomologous one. Other abnormalities: Chromosome breakage:

37. Fetal Testing Amniocentesis – the liquid that bathes the fetus is removed and tested Chorionic villus sampling (CVS) – a sample of the placenta is removed and tested Other techniques – ultrasound and fetoscopy, allow fetal health to be assessed visually in utero

38. LE 14-17a Amniocentesis Amniotic fluid withdrawn Fetus A sample of amniotic fluid can be taken starting at the 14th to 16th week of pregnancy. Centrifugation PlacentaUterusCervix Fluid Fetal cells Biochemical tests can be performed immediately on the amniotic fluid or later on the cultured cells. Biochemical tests Several weeks Karyotyping Fetal cells must be cultured for several weeks to obtain sufficient numbers for karyotyping.

39. LE 14-17b Chorionic villus sampling (CVS) PlacentaChorionic villi Fetus Suction tube inserted through cervix Fetal cells Biochemical tests Karyotyping and biochemical tests can be performed on the fetal cells immediately, providing results within a day or so. Several hours A sample of chorionic villus tissue can be taken as early as the 8th to 10th week of pregnancy. Karyotyping

40. Newborn Screening Simple genetic tests routinely performed in most hospitals in the United States Example Metabolic disorders such a phenylketonuria (PKU) -Autosomal recessive (Chromosome 12) -non-functional enzyme (phenylalanine hydroxylase) Inability to break-down essential amino acid phenylalanine--> build-up in blood causes mental retardation –Controlled by diet if caught early