Bio101 Ch11 Human Inheritance

EPISTASIS: So far:

one gene with complications. Now two genes affecting one character

In epistasis

a gene at one locus alters the phenotypic expression of a gene at a second locus

In Labrador retrievers, one gene sets pigment color:

B for black is dominant to b for brown

A second gene decides whether pigment is deposited:

in the hair at all: E allows it, ee blocks it

A dog with ee is yellow no matter what the first gene says

The second gene overrides the first

READING THE LABRADOR CROSS: Cross two BbEe dogs:

Four gamete types each, sixteen boxes — the same square you built Wednesday.

READING THE LABRADOR CROSS: But the ratio comes out 9 black : 3 brown : 4

yellow, not 9:3:3:1

Why 4? Because the 3 "brown-but-ee" and the 1 "black-but-ee" dogs all look the same — yellow.

READING THE LABRADOR CROSS: Two classes collapsed into one

The genotypes are still 9:3:3:1; the phenotypes are not.

Quantitative characters

vary along a continuum rather than in distinct classes — height, skin color, weight

polygenic inheritance:

the additive effect of two or more genes on one character

POLYGENIC INHERITANCE: In the model shown, three genes each contribute:

Each "dark-skin" allele adds a small increment of pigment.

AaBbCc × AaBbCc gives seven classes, from zero to six dark-skin alleles,

in a 1:6:15:20:15:6:1 distribution

A phenotype can depend on

the environment as well as the genotype

A genotype is generally associated

with a range of phenotypic possibilities, not one outcome

NATURE AND NURTURE:

These hydrangeas are the same genetic variety. The one on the right grew in acidic soil with free aluminum.

Characters shaped by many genes plus the environment are called

multifactorial

Same genes, different soil, different color

"Is it genetic?" is almost always the wrong question.

HUMANS ARE TERRIBLE SUBJECTS

Concept 11.4. Everything we have built, applied to people — and the method has to change

HUMANS ARE TERRIBLE SUBJECTS- Generation time is too long

Mendel got a new generation each year; we take 25

HUMANS ARE TERRIBLE SUBJECTS- Parents produce very few offspring

so the numbers are too small for clean ratios

HUMANS ARE TERRIBLE SUBJECTS- And breeding experiments would be unethical

We cannot assign mates.

HUMANS ARE TERRIBLE SUBJECTS- So we collect families that already exist and ____

analyze them after the fact

A pedigree

is a family tree showing a family’s history for a particular trait

PEDIGREE ANALYSIS- The symbols

squares are males, circles females, filled symbols show the trait, a horizontal line is a

mating

PEDIGREE ANALYSIS- ___ are listed left to right in birth order, under the couple that produced them. _____ are numbered down the left side

Offspring, generations

READING A PEDIGREE- A widow’s peak is a pointed hairline….

Is the allele dominant or recessive?

READING A PEDIGREE- Do not count filled symbols

frequency tells you nothing about dominance

READING A PEDIGREE- Look at the second generation

two parents with widow’s peaks have a daughter without one

READING A PEDIGREE

If the trait were recessive, two affected parents could not produce an unaffected child

READING A PEDIGREE- So widow’s peak is dominant

and both parents must be heterozygous, Ww

TRY THE SECOND ONE- PTC

is a chemical that some people taste as bitter and others cannot taste at all

TRY THE SECOND ONE- same question-

is the inability to taste PTC dominant or recessive?

TRY THE SECOND ONE- find the key generation-

two parents who can taste it(PTC) have a child who cannot

A trait that appears in a child of two unaffected parents is..

Both parents are Tt carriers(PTC)

PEDIGREES PREDICT

NOT PROMISE

PEDIGREES PREDICT, NOT PROMISE

Once you know the pattern, you can calculate the probability for a future child

PEDIGREES PREDICT, NOT PROMISE- Two Tt parents:

ach child has a 1 in 4 chance of being tt

PEDIGREES PREDICT, NOT PROMISE- But each conception is an independent event

Three unaffected children do not make the fourth safer.

PEDIGREES PREDICT, NOT PROMISE- A one-in-four chance means-

one in four every time, not one out of every four children.

RECESSIVELY INHERITED DISORDERS-

Thousands of genetic disorders are inherited as simple recessive traits, from mild to lethal

RECESSIVELY INHERITED DISORDERS- They show up only in individuals homozygous

for the allele

RECESSIVELY INHERITED DISORDERS- Albinism is the example in the figure-

the parents are both Aa and unaffected

RECESSIVELY INHERITED DISORDERS- Most children born with a recessive disorder have

two unaffected parents

that is the signature

A carrier

is a heterozygote: phenotypically normal, but able to transmit the recessive allele

CARRIERS- One quarter of the children are affected

and two thirds of the unaffected children are themselves carriers

CARRIERS- Work that second number out from the square

of the three unaffected boxes, two are Aa.

WHY RARE ALLELES STAY HIDDEN:

If a disease-causing recessive allele is rare, the chance of two carriers meeting and mating is low

WHY RARE ALLELES STAY HIDDEN- So the allele can persist for thousands of years

almost entirely inside healthy carriers

WHY RARE ALLELES STAY HIDDEN- Selection barely touches it

there is nothing visible to select against

Consanguineous matings-

between close relatives — raise the odds, because relatives are more likely to carry the same rare allele

CYSTIC FIBROSIS-

The most common lethal genetic disease in the United States: one in 2,500 people of

European descent

CYSTIC FIBROSIS- The allele is recessive

and about one in 25 people of European descent is a carrier

CYSTIC FIBROSIS- The normal allele codes for a membrane protein that transports chloride ions.

The defective version is absent or does not work.

CYSTIC FIBROSIS- THE RESULT

thick mucus in the lungs and pancreas, chronic infections, and digestive problems

CYSTIC FIBROSIS- One..

transport protein, a whole clinical syndrome. That is pleiotropy again.

Sickle-cell disease affects about

one in 365 African-Americans

SICKLE-CELL DISEASE

It is caused by the substitution of a single amino acid in hemoglobin

SICKLE-CELL DISEASE- at low oxygen,

the altered molecules aggregate into long fibers that deform the red blood cell into a sickle

Sickled cells carry less oxygen and jam in capillaries

anemia, pain, fever, organ damage

Heterozygotes are said to have sickle-cell trait

Usually healthy, with symptoms only at very low blood oxygen.

About one in ten

African-Americans has sickle- cell trait — unusually high for a harmful allele

SICKLE-CELL TRAIT AND MALARIA- The reason

a single copy reduces the frequency and severity of malaria

SICKLE-CELL TRAIT AND MALARIA

In malaria regions, heterozygotes out-survive both homozygotes.

Some human disorders are caused by dominant

alleles, and these behave very differently

A lethal dominant allele

is usually rare, because it kills the carrier before they reproduce — so it is not passed on

DOMINANTLY INHERITED DISORDERS- There are no silent carriers

if you have the allele, you have the condition.

So in a pedigree, a dominant disorder appears in every generation

no skipping

Achondroplasia

is a form of dwarfism caused by a rare dominant allele

ACHONDROPLASIA: look at the square

Dd × dd gives half Dd and half dd

Here is the detail that catches people — dd is the common genotype

99.99% of the population is homozygous recessive.

Dominant does not mean common

We said that Wednesday; here is the clinical version.

HUNTINGTON’S DISEASE

A degenerative disease of the nervous system, caused by a lethal dominant allele

HUNTINGTON’S DISEASE- So why has selection not removed it?

Because there are no symptoms until age 35 to 45 By then an affected person has usually already had children, and each child has a 50% chance of inheriting it.

A genetic test can tell you decades in advance

Whether to take it is a real and genuinely hard question.

MULTIFACTORIAL DISORDERS-

Heart disease, diabetes, cancer, alcoholism and many mental illnesses have both genetic and

environmental components

MULTIFACTORIAL DISORDERS- There is no single gene, and no simple pedigree

pattern

what you see is clustering, not a ratio

MULTIFACTORIAL DISORDERS- effect

Lifestyle has a tremendous effect on which phenotype actually appears

MULTIFACTORIAL DISORDERS- logic

Same logic as the hydrangeas. A genotype sets a range; the environment picks a point in it.

Genetic counselors

give prospective parents information when there is a family history of a

specific disease, They build the pedigree, identify the inheritance pattern, and calculate the probabilities

GENETIC COUNSELING

Each child is an independent event — the same point we made an hour ago

Carrier screening and fetal testing refine the numbers.

The counselor supplies the probabilities; the family makes the decision.

Epistasis

one gene masks another — 9:3:4 in Labradors

Polygenic inheritance

many genes add up to a continuum

Pedigrees

substitute for breeding experiments. Two unaffected parents with an affected child means recessive.

Recessive disorders

hide in carriers

Dominant disorders

appear in every generation