LOs

 Deduce information about genes, alleles, and gene functions from analysis of genetic crosses
and patterns of inheritance (pedigree analysis).
 Design genetic crosses to provide information about genes, alleles, and gene functions.
 Explain why it is advantageous to use true-breeding organisms in crosses.
 Predict progeny genotypic frequencies given the genotypes of the parental gametes.
 Identify an allele’s mode of inheritance from progeny phenotypes.
 Use statistical analysis to determine how well data from a genetic cross or human pedigree
analysis fits theoretical predictions.
 Draw a pedigree based on information in a story problem.
 Distinguish between dominant, recessive, autosomal, X-linked, and cytoplasmic modes of
inheritance.
 Calculate the probability that an individual in a pedigree has a particular genotype.
 Interpret the results of epistasis tests, comparing the phenotypes that result from single
mutations in two different genes with the phenotype of the double mutant.
 Determine if two mutations affect the same gene using complementation tests, and explain the
requirements and the basis for interpreting results from these tests.
 Define the terms incomplete penetrance, variable expressivity, and sex-limited phenotype, and
explain how these phenomena can complicate pedigree analysis.

Calculating probabilities
- Sum rule = adding up all probabilities of a given event
- Product rule = finding the probability of a combination of events by multiplying probabilities of
each event together
- Pedigrees show rare condts, assume people marrying in are not afflicted!!
Ex.

- Remember TSD is a very rare disease, unlikely that both grandparents on left side have it, go
with only one of them being a carrier bc that is most likely
- Daughter’s genotype
o 2/3 chance of Aa mother x ½ chance of passing on a  1/3 chance of Aa (carrier)
o 2/3 chance of AA (not carrier)
- Son’s genotype
o ½ chance of Aa father x ½ chance of passing on a  ¼ chance of Aa (carrier)
o ¾ chance of AA (not carrier)
- What is the probability of both the daughter and the son not being carriers?
o Probability of both being carriers: 1/3 Aa daughter x ¼ Aa son  1/12 chance
o Probability of only daughter carrier: 1/3 Aa daughter x ¾ AA son  3/12 chance
o Probability of only son carrier: 2/3 AA daughter x ¼ Aa son  2/12 chance
o Probability of neither being carriers: 2/3 AA daughter x ¾ AA son  6/12 chance
Chi-square analysis
- X2 = Σ (Obs – Exp)2/Exp, match up with a p value from Chi-square table
- DOF = number of offspring classes (varying parameters in experiment)
- Do not reject null hypothesis if p > 0.05 (expected deviation)

Readings notes
- Alleles do not always display the dominant/recessive relationship
- More than one gene tend to influence a phenotype
- Sex-linked traits eliminate possibility of heterozygosity
- Environment usually has influence on gene expression

Allele phenotypes
- Wild-type allele = normal, usually dominant (+)
- Loss of fxn mutation = null allele is made, cannot make gene product
- Gain of fxn mutation = often dominant when gene product is expressed
- Neutral mutation = gene product doesn’t affect phenotype/survival

Dominance
- Incomplete/partial dominance = the halved amount of enzyme product affects phenotype, leads
to blended phenotype that is nether dominant nor codominant
o Only one pair of alleles determines this genotype
o 1:2:1 F2 ratio
- Codominance = joint expression of both alleles in heterozygote
o Ex. MN blood group (M/N/MN)
o 1:2:1 F2 ratio
- Genes can have multiple alleles but each person can only inherit 2
o Ex. ABO blood group (IA/IB/i alleles)
o A and B are codominant, O is recessive to both
o Most people have normal alleles for FUT1 enzyme that creates H substance, a precursor
to A/B glycoproteins
o Type O are homozygous recessive (ii), can’t convert H substance to glycoproteins
o Type A can convert H substance to A antigen, type B converts H substance to B antigen,
type AB RBCs have a mix of both
o Bombay phenotype: person is type O due to having mutant FUT1 alleles, loss of fxn
mutation on that allele leads to no FUT1 enzyme made so even having A or B alleles will
not lead to A/B phenotype, but O phenotype instead (can still pass on A or B alleles)

Lethal alleles
- Recessive lethal alleles = homozygous recessive individuals do not survive
o Allele can be dominant in heterozygotes and change phenotype
o Behaving as recessive allele BUT is dominant wrt phenotype
o Ex. agouti gene: agouti wild type, yellow allele is phenotypically dominant but
recessively lethal (heterozygotes are yellow, homozygous recessive do not survive)
o 2:1 F2 ratio
- Dominant lethal alleles = one copy of allele result in individuals not surviving

Gene interaction
 - Often, a phenotype is affected by more than one gene and their products
- Epigenesis = feature that is under the control and influence of many genes
o If F2 ratio comes out in sixteenths, consider 2 gene pairs involved (dihybrid cross)
o When calculating probabilities, consider probabilities of each assorted gene separately!
- Epistasis = expression of one gene pair masks/modifies the effect of another gene pair
o Epistatic gene product does the masking, hypostatic get masked
o Can have dominant or recessive epistasis depending on how many mutant alleles are
needed to mask the hypostatic gene product
o 2 gene pairs can COMPLEMENT each other when at least one dominant allele in each
pair is needed to express a certain phenotype
 Ex. FUT1 gene and A/B gene

Modified F2 phenotypic ratios and possible gene interactions

- Recessive epistasis
o 9:4:3
o Precursor –(A) intermediate –(B) product
o A-B- leads to product, A-bb leads to intermediate, aaB- and aabb leads to precursor
o Need at least one dominant allele for gene A to have product
- Dominant epistasis
o 12:3:1
o Precursor1 –(A) product1; precursor2 –(B) product2 (product1 is dominant)
o A-B- and A-bb lead to product1, aabb leads to precursor1, aaB- leads to product2
o Product of a separate gene masks product of second gene
- Complementary gene interaction
o 9:7
o Precursor –(A) intermediate –(B) product
o A-B- leads to product, everything else (aaB-,A-bb,aabb) leads to precursor/intermediate
that give the same phenotype
o At least one dominant allele is needed for either gene to have final product
o (Can also think of A and B as subunits making enzyme dimer)
- Complementation analysis (to find out if 2 mutations are producing a similar phenotype)
o Ex. more than one gene affects wing developmt in flies. Are two given mutations on the
same locus affecting wing developmt or on different loci and still producing wingless F1?
o M1 x M2  + (AAbb x aaBB  AaBb)
 M1 and M2 are recessive and on separate genes, they complement each other
in restoring the wild type phenotype
o M1 x M2  wingless (a1a1 x a2a2  a, not +)
 M1 and M2 are on the same gene, complementation does not occur because
the wild type phenotype is not restored
- Other ratios such as 10:3:3 are possible. DRAW OUT POSSIBLE ENZYME PATHWAYS
- Redundancy
o 15:1
o Precursor1 –(A) product; precursor2 –(B) product
o Both precursors can lead to product when corresponding enzyme is present
o As long as individual has at least one dominant allele for either gene, product is made
- Control of an enzyme
o 13:3
o Gene1  enzyme A; precursor –(A) product
 o Gene2  modulator B; G1  A –(B) blocked A, cannot turn precursor to product
o Expression of gene2 makes modulator B that blocks conversion pathway from precursor
to product by modulating enzyme A
o A-B- give precursor, aaB- gives precursor, A-bb gives product, aabb gives product

X-linkage
- Genes that are on the X chromosome have patterns of inheritance differing between genders of
parents with mutations and genders of offspring
- Males express x-linked mutations bc they only have one x chromosome, cannot be carrier
- Females can be carriers of recessive x-linked mutations bc they have 2 x chromosomes
- Males are hemizygous bc they only have one copy of the gene while being diploid

The 3 phenomena that complicate pedigree analysis:

- Sex-limited inheritance
- Penetrance
- Expressivity

Sex-limited inheritance
- NOT sex linkage
- Autosomal inheritance but only expressed in one of the genders
- Ex. genotype for milking offspring is in all individuals BUT only women can express that
phenotype; men who also have the gene cannot

Penetrance and expressivity

- Penetrance = degree of expression of a mutant genotype in the offspring ratio
o Ex. if 15/100 mutant offspring express the mutant phenotype, the mutant gene has a
penetrance of 15%
- Expressivity = range of expression of the mutant genotype in the offspring
o Ex. all mutant offspring for eyelessness can have varying eye sizes; some are completely
eyeless while some have reduced eye size
Position effects
- Genes can be displaced by translocation/inversion
- If genes are near heterochromatin (condensed, more inert chromatin), they are less transcribed
and that decrease in gene product has an effect on phenotype

Temperature effects
- Temperature-sensitive mutations are determined by envmtal temperature
- Ex. Siamese cats that have pigmented phenotype on regions of body with lower temperature

Nutritional effects
- Ex. lactose intolerance preventing person from digesting lactose
- Phenotype of lactose intolerance can be eliminated if lactose is eliminated from diet

Gene imprinting and silencing

- Imprinting = different DNA methylation patterns between maternal and paternal gametes;
imprinted allele is silenced and only the other inherited allele is expressed
 - Selective silencing of genes occurs during early developmt depending on parental genes
- Imprinting in the next generation depends on gene inheritance through sperm-producing or
egg-producing tissue (of mother or of father)

Modifications to Mendelian ratios

Ex. Blindness in cave fish from different isolated caves

- 1 and 2 do not complement, 3 and 5 do not complement, 4 always complements

- Therefore, there are at least 3 genes involved to produce sight: gene for 1 and 2, gene for 4,
gene for 3 and 5

- Assume homozygous, truebreeding parents (bc isolated for millennia, interbreeding)

- Cannot use blind offspring for complementation testing bc it is heterozygous!
- The allele for blindness here is dominant