1. José A. Cardé, PhD Universidad Adventista de las Antillas Agosto 2011

2.  Allelic Variation and Gene Function  Gene Action: From Genotype to Phenotype  Inbreeding: Another Look at Pedigrees

3.  Mendel’s traits showed two distinct forms  Most genes do not exhibit simple inheritance  Genotypic ratios persist but phenotypic ratios may vary due to “outside-the-gene” influences including - Multiple alleles - Gene linkage - Epistasis - Codominance, - Incomplete penetrance - Environment

4. The diverse kinds of alleles of genes affect phenotypes in different ways.

5.  Each trait that Mendel studied was controlled by a single gene with two alleles.  Genes may have more than 2 alleles.  Different alleles may affect the phenotype in different ways.

6. Incomplete Dominance The heterozygous phenotype is between those of the two homozygotes Example: Familial hypercholesterolemia (FH) - A heterozygote has approximately half the normal number of receptors in the liver for LDL cholesterol - A homozygous for the mutant allele totally lacks the receptor, and so their serum cholesterol level is very high

7.  The phenotype of the heterozygote is midway between the phenotypes of the two homozygotes.  One allele is partially, or incompletely, dominant over the other.

8. Codominance The heterozygous phenotype results from the expression of both alleles The ABO gene encodes a cell surface protein - I A allele produces A antigen - I B allele produces B antigen - i (I O ) allele does not produce antigens Alleles I A and I B are codominant between them, and both are completely dominant to i

9. Figure 5.3

10.  The heterozygote expresses the phenotypes of both homozygotes.  Neither allele is dominant.

11. Figure 5.4 Offspring from Parents with Blood Type A and Blood Type B Figure 5.4

12. Multiple Alleles  An individual carries two alleles for each autosomal gene  However, a gene can have multiple alleles because its sequence can deviate in many ways  Different allele combinations can produce variations in the phenotype  - PKU gene has hundreds of alleles resulting in four basic phenotypes  - CF gene has over 1500 alleles

13.  The most common alleles in nature is the wild-type allele.(+/+)  All other alleles are mutants.(ch,h,0)  The gene is represented with the letter of the mutant (c)

14. Alelos Múltiples : Tipos de Sangre ABO

15.  An allelic series describes the dominance hierarchy of multiple alleles.  A null allele is nonfunctional.  A hypomorphic allele has partial function. Relación funcional entre miembros de grupo de alélos múltiples

16.  Visible mutations - color o textura, muchas recesivas, pocas dominantes  Sterile mutations- limitan las reproducción, dom o reces, afectan ambos sexos o a uno de los dos  Lethal mutations - interfieren con funciones vitales, muerte

17. Lethal Alleles A lethal genotype causes death before the individual can reproduce - This removes an expected progeny class following a specific cross A double dose of a dominant allele may be lethal - Examples: - Achondroplastic dwarfismAchondroplastic dwarfism - Mexican hairless dogs - Brachydactyly, recesive homocigote

18. Figure 5.1b Figure 5.1 Lethal Alleles

23.  Genes often have multiple alleles.  Mutant alleles may be dominant, recessive, incompletely dominant, or codominant.  If a hybrid that inherited a recessive mutation from each of its parents has a mutant phenotype, then the recessive mutations are alleles of the same gene; if the hybrid has a wild phenotype, then the recessive mutations are alleles of different genes.

24.  Most genes encode polypeptides.  In homozygous condition, recessive mutations often abolish or diminish polypeptide activity.  Some dominant mutations produce a polypeptide that interferes with the activity of the polypeptide produced by the wild-type allele of a gene.

25. Phenotypes depend on both environmental and genetic factors.

26.  Genes function in a biological and physical environment.  Examples  Drosophila shibire mutation (temperature)  Phenylketonuria (diet)  Pattern baldness (gender)

27. Penetrance and Expressivity Penetrance refers to the all-or-none expression of a single gene Expressivity refers to the severity or extent A genotype is incompletely penetrant if some individuals do not express the phenotype A phenotype is variably expressive if symptoms vary in intensity among different people

28.  Individuals do not express a trait even though they have the appropriate genotype.

29.  A trait is not manifested uniformly among individuals that show it.

30. Penetrance and Expressivity Penetrance refers to the all-or-none expression of a single gene Expressivity refers to the severity or extent A genotype is incompletely penetrant if some individuals do not express the phenotype A phenotype is variably expressive if symptoms vary in intensity among different people

31. Epistasis The phenomenon where one gene affects the expression of a second gene Example: Bombay phenotype - The H gene is epistatic to the I gene - H protein places a molecule at the cell surface to which the A or B antigens are attached - hh genotype = no H protein - Without H protein the A or B antigens can not be attached to the surface of the RBC - All hh genotypes have the phenotype of type O, although the ABO blood group can be anything (A, B, AB, or O)

32. Epistasis

33.  In epistasis, an allele of one gene overrides the effect of other genes on the phenotype.  In Drosophila,  The cinnabar mutation produces bright red eyes.  The white mutation produces white eyes.  When both mutations are present in the same fly, the eyes are white.  The white mutation is epistatic to the cinnabar mutation.

34.  Different combinations of alleles from two genes result in different phenotypes.  In this example, R-P- produces walnut R-pp produces rose rrP- produces pea rrpp produces single

35. Rose RRpp y Pea son rrPP - F1 = RrPp = Walnut F2 – 9/16 R_P_: 3R_pp, : 3rrP_:1 rrpp Demuestra que dos genes q se sortean independientes pueden afectar un mismo rasgo

40.  A gene that affects many phenotypes is pleiotropic.  Mutations in the phenylketonuria gene cause mental impairment, light hair color, and the presence of metabolites in blood and urine.  Mutations in the Drosophila singed gene affect bristle shape and egg production.

41. Pleiotropy  The phenomenon where one gene controls several functions or has more than one effect  Example: Porphyria variegata - Affected several members of European Royal families, including King George III - The varied illnesses & quirks appeared to be different unrelated disorders

42. Photo © North Wind Picture Archives Figure 5.5a Figure 5.5b Pleiotropy Figure 5.5

43. Figure 5.6

44. Figure 5.7

45.  Gene action is affected by biological and physical factors in the environment.  Two or more genes may influence a trait.  A mutant allele is epistatic to a mutant allele of another gene if it has an overriding effect on the phenotype.  A gene is pleiotropic if it influences many different phenotypes.

46. Geneticists use a simple statistic, the inbreeding coefficient, to analyze the effects of matings between relatives.

48.  Inbred lines of experimental species are often less vigorous than hybrid lines.  Inbred lines of self- fertilized plants are homozygous for alleles that were present in the founding line.

49.  When two different inbred lines are crossed, the hybrids are heterozygous for many genes.  These heterozygotes display heterosis, or hybrid vigor.

50.  Individuals A and B are half-siblings.  Their offspring, I, is inbred, and inherited one copy of her genes from A and one copy from B.  These copies may be identical by descent if they are identical copies inherited from individual C.  C is the common ancestor of I.

51.  The Inbreeding Coefficient, F, is the probability that the two gene copies in an individual are identical by descent from a common ancestor.  Calculation of the Inbreeding Coefficient 1) Identify the common ancestor(s) of an inbred individual. 2) Count the number of individuals (n) in each inbreeding loop. 3) Calculate the quantity (1/2) n for each inbreeding loop and sum the results.

52. Insert Unmarked Figure Figure number Chapter 4 p. 725 top left 1) Identify the common ancestor(s).  C is the common ancestor, so there is one inbreeding loop. 2) Count the number of individuals in each inbreeding loop.  The Loop includes C, A, and B; n=3 3) Calculate (1/2) n for each loop and sum the results.  There is only one loop in this case  (1/2) 3 = 1/8, so F = 1/8

53. 1) Identify the common ancestor(s).  U and V are both common ancestors, so there are two inbreeding loops. 2) Count the number of individuals in each inbreeding loop.  Loop 1: U, R, S; n=3  Loop 2: V. R, S; n=3 3) Calculate (1/2) n for each loop and sum the results.  Loop 1: (1/2) 3 = 1/8  Loop 2: (1/2) 3 = 1/8  F = 1/8 + 1/8 = 1/4

54. Insert Unmarked Figure Figure Number p. 726 top left (in- text art) De donde sale el 1/8: 1/8 es la p de que cualquiera de los alelos sea heredado al individuo I; ¼ por A y ¼ por B; y 1/16 para uno de los alelos y 1/16 para el otro. De donde sale el 1/8?:

55.  Multiply (1/2) n by the term [1 + F CA ] F T = (1/2) 3  [1 + (1/2) 3 ] = 1/8  (1 + 1/8) = 9/64

56. RESUMEN

58.  Calculate the fraction of genes that two relatives share  Calculate the inbreeding coefficient for the offspring of a mating between the two relatives  The coefficient of relationship = F  2  For full siblings, F = 1/4, so the coefficient of relationship is 1/2  This means that full siblings share 1/2 of their genes

59.  Inbreeding increases the frequency of homozygotes and decreases the frequency of heterozygotes.  The effects of inbreeding are proportional to the inbreeding coefficient, which is the probability that two gene copies in an individual are identical by descent from a common ancestor.  The coefficient of relationship is the fraction of genes that two individuals share by virtue of common ancestry.