Modification of Mendelian Ratio

1
Chapter 4

• Modification of Mendelian Ratio

2
Alleles Alter Phenotype

• Alter phenotype in different ways
• may be under the influence of 1 or more genes at
  a specific loci or 1 or more pairs of homologous
  chromosomes
• Most common allele in the population is called
  the wild type, usually the dominant form but not
  necessarily
• standard by which we compare all mutations

3
Mutations

• May alter the gene product must cause a change
  in the phenotype
• functional activity change in the gene product
• often see a loss of function loss of function
  mutation
• if loss of function is complete null allele
• can see an enhancement of function and an
  increase in quantity of the gene product gain
  of function usually deals with gene regulation
• protooncogene regulates cell cycle can be
  converted to an oncogene can cause a cancer
  cell
• Mutation may not detectably alter function see
  only in the DNA sequence
• Traits are often influenced by 1 gene complex
  metabolic pathways mess up one enzyme results
  in no end product

4
Genetic Symbols

• Recessive allele lowercase and italic
• Dominant allele uppercase and italic
• In fruit flies use initial or 2-3 letters of
  mutant trait
• recessive is still lowercase, wild type is the
  same letters but with a superscript
• ebony is recessive body color e
• gray is wild-type body color e
• / indicates that 2 allele designations of same
  locus on 2 homologous chromosomes
• can also summarize as /, /e, e/e, gray homo,
  gray hetero, ebony homo respectively
• Also when one allele isnt dominant use
  uppercase letter and superscripts of alternative
  alleles R1 or R2
• Bacteria and yeast use lowercase letters to ID
  genes and capital letter when talking of gene
  product, human genes use all capital letters to
  ID genes

5
Incomplete or Partial Dominance

• When cross 2 true-breeding parents, get an
  intermediate phenotype because neither allele is
  dominant
• Heterozygous offspring are different from the
  parents
• Break from convention to name the allele
• R1 red
• R2 white
• Phenotypic and genotypic ratios are the same

6
Tay-Sachs Disease

• Clear cut incomplete dominance is rare
• Tay-Sachs disease is a lipid storage disease that
  has an inactive enzyme hexosaminidase required
  for lipid metabolism
• homozygous recessive is fatal
• heterozygous people have no symptoms of disease
  even with only 50 of enzyme activity

7
Co-Dominance

• Both alleles influence phenotype see 2
  detectable gene products that are different
• expression of both alleles in heterozygote is
  co-dominant
• see in MN blood group have alleles for M or N
  but may see M, N or MN on red blood cells
  depending on homo- or hetrozygocity
• see 3 phenotypes corresponding to 3 genotypes

8
Multiple Alleles in Population

• Each mutation in gene produces a different allele
  not restricted to 2
• 3 or more alleles in population generates a
  multiple allele can study in the population
• individual can have 2 homologous gene loci that
  may have different alleles

9
ABO Blood Group

• 3 alternative alleles of 1 gene presence of Ag
  (glycolipid) on surface of RBC (not same as MN)
  that yields 4 different phenotypes A, B, AB or
  O (no Ag on RBC)
• 3 alleles IA, IB and IO (I isoagglutinogen)
• 6 genotypes - IAIA, IAIB, IAIO, IBIB, IBIO, and
  IOIO
• IA and IB are dominant to IO
• Useful in blood transfusion and organ transplant

10
Bombay Phenotype

• A and B are glycolipids on the surface of the RBC
  with different terminal sugars derived from
  H-substance
• Bombay phenotype occurs when H-substance doesnt
  completely form so cant add sugars, appear to be
  group O
• FUT1 is gene for H-substance

11
Fruit Fly white Locus

• Various alleles at white locus recessive
  mutation to cause white eyes
• Colors can range from ruby to orange to buff
  dependent on allele present
• 20 less pigment than in wt eyes (brick red)

12
Lethal Alleles

• Lethal alleles represent essential genes
• Mutations in genes that lead to nonfunctional
  products can be tolerated in heterozygotes if wt
  allele can make enough of the essential product
  to allow survival
• Recessive lethal alleles in homozygous
  individuals will not survive time of death is
  dependent on when the gene product is required
• May result in distinct mutant phenotype when
  heterozygous

13
Agouti Coat in Mice

• Agouti is the brownish-gray mouse coat
• Mutation yields a yellow coat color -
  AY, homozygous recessive lethal but
  dominant with respect to phenotype
• 2 copies will result in death before birth

14
Other Cases

• Other lethals behave dominantly and just 1 allele
  will result in death
• Dominant lethal alleles rarely observed as many
  die prior to reproductive age
• Huntingtons disease dominant allele but
  disease doesnt show up until late adulthood (40
  years)
• may have already spread to offspring before
  knowing that they have the disease

15
2 Gene Pairs with 2 Modes of Inheritance

• Dominant distribution x co-dominant or incomplete
  dominance distribution will alter the 9331
  ratio of phenotypes
• Easy to use the forked line method to determine
  the ratio

16
Phenotype Affected by 1 Gene

• Genetic influence is more complex than Mendels
  stuff many genes and their products influence
  phenotype
• Gene interaction idea that several genes
  influence a particular characteristic may not
  interact directly with one another
• Cellular function of numerous gene products
  contribute to development of common phenotype
• fly eye structure is complex and a cascade of
  developmental events leading to formation
• Epigenesis each step of development increases
  complexity or sensory organ under influence of
  more than 1 gene

17
Epistasis

• Epistasis expression of one gene or gene pair
  masks or modifies expression of a gene or gene
  pair
• may be antagonistic, exert influence on one
  another in a complementary or cooperative fashion
• Homozygous presence of recessive allele
  prevents/overrides expression of alleles at 2nd
  locus
• 1st locus is epistatic and 2nd locus is
  hypostatic to the 1st locus

18
Bombay Phenotype

• FUT1 masks IA and IB
• Need 1 wild-type to get A or B otherwise O type
• Yields a ratio of 3A6AB3B4O in offspring
• Important to note the following
• only one characteristic blood type is being
  followed (before we followed both gene pairs)
• follow 1 trait but still express in 16ths still
  confident that 2nd gene pair is involved in
  phenotypic expression

19
Other Mendelian Modifications

• Can modify the classical 9331 ratio if
  epistasis combines with one of the 4 phenotypes
• Need to make several assumptions

20
Assumptions

• Distinct phenotypic classes are produced
  describable from all others, discontinuous
  variation, where phenotypic categories are
  discrete and qualitatively different from one
  another
• Genes considered are not linked and assort
  independently Aa and Bb
• Assume complete dominance AA and Aa BB and Bb
  are equivalent in genetic effects
• use A-B- - either allele may be in the blank
  without consequence to phenotype
• All P1 are homozygous individuals, F1 generation
  are heterozygous
• F2 generation is main focus of analysis
• 9/16 A-B- 3/16 A-bb 3/16 aaB- 1/16 aabb
• dominance all genotypes in each category have
  equivalent effect on phenotype

21
Various Phenotypes Influenced by Epistasis
22
Coat Color in Mice Case 1

• A- agouti color (normal) black color is
  converted to agouti
• aa black made from colorless substance
• bb albino at a different gene loci to eliminate
  pigment
• happens regardless of the A loci dominance
• recessive control
• 9/16 A-B- 3/16 A-bb 3/16 aaB- 1/16 aabb will
  yield a phenotype of 9 agouti, 3 black and 4
  albino
• Epistasis bb masks expression of A gene

23
Summer Squash Case 2

• Dominant A allele blocks color at a 2nd locus
• A present get white fruit regardless of B gene
• aa and either BB or Bb yellow fruit
• aa and bb green fruit
• Modified ratio is 1231

24
Sweet Pea Flowers Case 3

• 2 true breeding white flowered sweet peas, F1
  is all purple flowers and F2 9/16 purple and 7/16
  white
• Need 1 dominant allele in 2 gene pairs to have
  purple flowers because homozygous condition of
  either allele masks expression of dominant allele
• AAbb (white ) x aaBB (white) AaBb (purple)
• 9/16 A-B- purple 3/16 A-bb white 3/16 aaB-
  white and 1/16 aabb white
• Need one dominant allele from each gene pair to
  make final biochemical product purple pigment
• 2 genes interact to influence development of a
  common phenotype
• other examples 2 genes control phenotype

25
Novel PhenotypesCase 4

• Other gene interactions yield new phenotypes and
  modified dihybrid ratios
• Disc shaped fruit (AABB) and long fruit (aabb)
• F1 all disc shaped
• F2 see a sphere shape along with disc and long
• A-B- disc A-bb and aaB- sphere aabb long
  ratio is 961, both genes influence fruit
  shape equally
• if dominant of each gene it is long, if one gene
  is recessive then it is sphere and in both genes
  are recessive then long

26
Cases 5-8

• Require additional modifications and other gene
  interactions
• 2 things in common
• havent violated any principles of segregation
  and independent assortment (Mendels conclusion
  still valid)
• F2 phenotype ration is expressed in 16ths
  indicates 2 genes involved (assumed by
  geneticists)

27
Complementation Analysis

• How can you determine if 2 mutations causing a
  similar phenotype are alleles of same gene
• 2 mutations arise and both produce similar
  phenotypes identified separately
• wingless fruit flies - ? mutation in the same
  gene or in 2 of the many genes involved in wing
  formation
• use complementation analysis

28
Complementation Analysis

• Cross 2 mutant strains and analyze the F1
  generation
• 2 outcomes and interpretations
• ma mutation 1 mb mutation 2

29
Mutation 1

• Cross mutation 1 and 2 and come up with all
  offspring having normal wings
• Interpretation mutations are in different genes
  
• complementation occurs to and flies are
  heterozygous at both loci make normal gene
  products to make normal wings

30
Mutation 2

• Cross mutation 1 and 2 and come up with all
  offspring failing to develop wings
• Interpretation mutation is in the same gene and
  are alleles to one another
• no complementation flies are homozygous for 2
  mutant alleles
• no normal gene products means no wings

31
Screen for Mutations

• Complementation analysis can screen for any
  number of individual mutation resulting in same
  phenotype
• single gene to more genes
• Complementation group all mutations present in
  any single gene complement mutations in all
  other groups
• Can use to determine the total number of genes
  involved in determination of trait