Transcript Variation, probability, and pedigree

Variation, probability, and pedigree
• Gamete production is source of variation and
genetic diversity, an advantage of sex.
– As a result of segregation and independent
assortment, lots of combinations possible.
– 2n possibilities exist for diploids where n = haploid
number of chromosomes
• In humans, this is 8 million different gametes
– Crossing over during meiosis creates even more
combinations of genetic information
– This diversity important in evolution, survival.
1
Product law
2
• Product law used to calculate odds of an
outcome from independent events
– Flip a coin: heads or tails, 50:50 chance (1/2)
– Flip a coin 3 times, get 3 heads; the next flip, there’s
still a 50:50 chance of getting a head.
– The chance of getting 4 heads in a row:
• ½ x ½ x ½ x ½ = 1/16 the product law.
– Odds of round, yellow seeds in a cross of Ww GG x
Ww gg: ¾ x 4/4 = 3/4
Sum Law
• The sum law: outcomes of
events are independent, but can
be accomplished in more than
one way.
Flip a penny and a nickel:
odds of 1 heads and 1 tails?
There are 4 possible outcomes from this flip.
1 head, 1 tail can be from the penny being heads (odds
1/4), but also from the nickel (1/4): ¼ + ¼ = ½
3
Human genetics
• How to determine inheritance of a trait in
humans
– Can’t (shouldn’t) mandate breeding partners
– Low numbers of offspring.
• Pedigrees
– Follow inheritance of trait in families
– Compare results to other families
– Draw conclusions.
4
Key to pedigrees
5
Pedigree sample-1
*Look for things you know
must be true.
• Look at inheritance of trait
expressed by shaded
individual.
• You KNOW that it can’t be
dominant because at least 1 of
the parents would also have to
show that phenotype.
6
Pedigree sample-2
• Beware of things that seem
logical but might NOT be true.
• The Shaded trait is dominant.
– “A” dominant, “a” recessive
• The mother must be aa.
•The father, however, may or may not be homozygous:
If the father is AA, you would expect all offspring to be
Aa (AA x aa = Aa); this is what appears to be true.
7
continued
BUT, if the father is Aa, the odds for
each child showing the dominant
phenotype is 50:50.
Just like you can flip a coin 3 times
and get heads each time, you could
get 3 children that are all Aa,
showing the dominant phenotype.
The father COULD be Aa. Likely?
No. Possible? Definitely.
8
Pedigree problem from text
A and a are
alleles. Which
is shaded?
What are the
genotypes?
Find the sure
things first.
II 6 must have a recessive trait, being unlike both
parents (who must be heterozygous).
9
Modification of Mendel
10
• Definitions and terms from Chap. 4
– Autosomes vs. sex chromosomes
– Wild-type: “normal”, usually dominant
• Dominant does NOT mean most common
• Examples: e+/ e where e+ is wild type, slash
separates alleles from homologs
– Lower case “e” means recessive
• Wr+/ Wr shows mutant phenotype because Wr is
a dominant mutant allele
– R1 & R2; IA & IB; leu-; etc.
– DnaA is a protein, dnaA is the gene!!
Mutation and phenotype
• Mutations are the source of new alleles
• A new allele may result in a new phenotype
because of changes in enzyme activity
– Enzyme usually has decreased or no activity
– Enzyme may have increased activity
• usually, change in a regulatory gene
– Enzyme may be unaltered despite change in DNA
• Allele only at DNA level, no other phenotype
11
Alterations to Mendel
•
•
•
•
•
•
•
•
Incomplete or partial dominance
Codominance
Multiple alleles
Lethal alleles
Gene interactions
Sex-linked, sex-limited, & sex-influenced
Effect of environment
Extranuclear inheritance
12
Incomplete or partial dominance
One allele only
partially masks the
other.
Half as much
enzyme makes half
as much pigment.
Phenotypic ratio is
the same as
genotypic: 1:2:1
www.people.virginia.edu/ ~rjh9u/snapdragon.html
13
Partial dominance-2
14
• Partial dominance is not common
– A molecular phenotype showing partial dominance
is more common
– One allele instead of 2 is producing enzyme, so on
a gel, a protein band is half as intense.
Codominance
• M and N blood groups: LM
LN
– Glycoprotein on blood cell
surface
– If one of each allele, both
expressed.
– Phenotype = genotype,
essentially
– Heterozygote cross:
shows 1:2:1 ratio
http://boneslab.chembio.ntnu.no/Tore/Bilder/BlodMN.jpg
15
Multiple alleles
16
• In peas, Mendel following the inheritance of two
contrasting traits, e.g. purple vs. white flowers
• Often, more than two alleles for a trait exist.
• Study of multiple alleles requires a population!
– In diploid organisms, an individual can only have a
maximum of two alleles. (2 different alleles)
– In populations, many different alleles may be
present.
– Classic example: the ABO blood group system
ABO Blood groups
Series of sugars added to
cell lipid creates trait.
Genotypes include:
AA, AO = type A
BB, BO = type B
OO = type O
AB = type AB where
A and B are co-dominant,
O is recessive, and the blood
type is the phenotype.
http://science.uwe.ac.uk/StaffPages/na/abo_ho2.gif
17
Lethal alleles
18
• In genetic crosses, information is obtained by
examining the phenotype of the offspring.
– In some instances, the phenotype is lethal
– Lethality may present itself late in life
(Huntington Disease) or may result in no
offspring.
– Example:
Fur color in mice:
Agouti on left, yellow on right.
http://www.cumc.columbia.edu/news/in-vivo/Vol1_Iss21_dec18_02/img/obesity-mice.jpg
Lethal alleles-2
19
– If certain genotypes are lethal, results of a cross
may be quite confusing.
• Agouti x agouti = all agouti
• Yellow x yellow = 2/3 yellow, 1/3 agouti
• Agouti x yellow = ½ yellow, ½ agouti
– 2:1 ratio is tip-off that something odd happens
– Homozygous for yellow is lethal, so that genotype is
NOT represented.
– For lethality, yellow allele acts as recessive.
– For coat color, yellow allele acts as dominant
• A = agouti, Ay = yellow. Heterozygote is yellow.
Complex inheritance and dihybrid crosses
• Book example: inheritance of simple trait and
multiple allele trait: albinism and ABO
– Crossing of heterozygotes (blood group AB)
– Assume independent assortment
– Simple trait shows 3:1 ratio, co-dominant trait
shows 1:2:1 ratio
– Phenotypic classes in offspring no longer 9:3:3:1
• Actually come out 3:6:3:1:2:1
• Complex inheritance produces odd ratios.
20