Lecture 5: Pedigree Analysis

T/f: can test crosses be used to determine inheritance patterns

t: yes BUT can’t be used to study human gene inheritance

what are the four possible modes of inheritance of a trait that are controlled by a single gene:

• autosomal dominant

• autosomal recessive

• sex-linked dominant

• sex-linked recessive

t/f: can test crosses be done for humans

no → can’t morally selectively breed humans

t/f: can punet squares be used for humans

yes → can still use punnet squares for humans just not test crosses

what is used to study inheritance patterns in humans

pedigrees

what are pedigrees

used to study inheritance patterns in humans

• basically a diagram of family’s relevant genetic features (looks like family tree)

• keeps record of matings and genetic conditions

how are pedigrees analyzed

using Mendel’s laws

how are Mendel’s laws used Mendel’s laws used to analyze pedigrees

• is a trait determined by alternate alleles of a single gene

• is a trait dominant or recessive

do these symbols mean

diff symbols for people who are carriers → heterozygous for a recessive trait

what do these symbols mean

unaffected…

• male

• female

• sex unspecified

what do these mean

male, female, sex unspecified have multiple progeny (offspring)

male deceased, female deceased

consanguineous mating → mating btwn closely related individuals (can increase probability of certain diseases occurring so is kept track of)

• sibship line

• line of descent

• individual number w in generation

• generation 2

• mating line

• generation 1

• monozygotic

• affected

• sibling

• male

• female

• mating

• descent

• dizygotic

• death

• carrier

• generation

• carrier

• consanguineous mating

what are some differences btwn breeding experiments and pedigrees

breeding experiments

• inbred bloodlines (P, F1, F2, etc.)

• no “new” individuals introduced"

pedigrees

• new individuals added each generation

• not everyone in pedigree is a descendant of someone else in the pedigree

many human traits run in families, but most do not show simple mendelian inheritance. Why?

most human traits are not determined by a single gene

• most confirmed single-gene traits in humans are rare

even with single-gene traits, determining inheritance patterns in humans can be challenging compared to peas. Why?

• environmental effects

• human’s don’t produce hundreds or thousands of offspring

what are mendel’s laws? explain them

1. Mendel’s Law of Segregation: the 2 alleles (in a diploid organism) for each trait separate during gamete formation, then unite at random, one for each parent, at fertilization (depend on each other)

2. Mendel’s Law of Independent Assortment: describes how diff alleles of diff genes behave (independent from each other)

3. Mendel’s law of product: the probability of 2 or more independent events occurring together is the product of the probabilities that each event will occur by itself (independent AND together = product)

4. Mendel’s law of sum: the probability of either of 2 mutually exclusive events occurring is the sum of their individual probabilities (one AND/OR the other)

what are 3 examples of single-gene traits in humans

albinism

• missing enzyme for melanin production

• unpigmented skin, hair, eyes

cystic fibrosis

• non-functional CFTR gene (resopnsible for regulating movement of salt/water in/out of cells)

• organs become clogged w thick mucous, which interferes w breathing and digestion

huntington disease

• abnorma protein important for neurons

• progressive neurological damage

what type of trait is albinism? explain why

usually recessive epistatic

• epistatic meaning it masks the effect of another gene (that codes for albinism)

• recessive meaning needs both copies of allele to code for albinism for it to be there

2 types of melanin → eumelanin (darker pigment) and pheomelanin (lighter pigment)

having 2 copies of it messes up the enzyme that makes eumelanin (dark one)

what type of trait is cystic fibrosis? explain why

recessive cystic fibrosis disease allele encodes abnormal CFTR protein

• CFTR protein regulated passage of chloride ions across cell membrane

• heterozygous individuals produce enough CFTR for normal lung fx

  • :. mutant cystic fibrosis-causing allele is recessive to wildtype allele

what type of pattern of inheritance is indicative of a rare recessive trait

rare recessive trait = infected individuals are rare, but abundant in one generation

hence, horizontal pattern of inheritance

• parents are often carriers instead of actually having the disease

which type of inheritance pattern can “skip” generations

horizontal

what is a genetic disease that is an example of a horizontal inheritance pattern

cystic fibrosis

what type of trait is huntington disease? explain why

dominant trait → abnormal Htt protein damages nerve cells even when normal proteins are already present (hence why huntington’s allele is dominant

why is huntington’s disease still prevalent even despite what type of trait it is and it’s fatal nature

it is a dominant trait → if you have even one copy of the allele you will have the disease BUT is still prevalent bc it is usually only fatal AFTER the person has had the chance to reproduce

• there is more than one mutant allele for the disease → larger insertions in the gene lead to earlier onset disease

what type of inheritance pattern does huntington’s disease have? why?

vertical inheritance pattern

• every affected person has at LEAST one effected parent

• doesn’t skip generations bc dominant

  • if you have at least one copy you have the disease, :. to pass it on you HAVE to have it

in which disease is mating btwn an affected and unaffected person basically a test cross

huntington disease

• can determine by phenotype of child if carrying parent is likely to be homo or heterozygous

why are there no carriers of dominant traits

if individual has 1 copy of the allele, they have the trait

how can dominant traits be recognized in pedigrees

hint: 3 key characteristics

3 key characteristics:

1. affected children always have at least one effected parent

2. ^so dominant traits show a vertical inheritance pattern

3. two affected parents can produce unaffected children, if both parents are heterozygous

how can recessive traits be recognized in pedigrees

hint: 3 key characteristics

1. affected individuals can be children of two unaffected carriers (particularly happens as a result of consanguineous mating)

2. all children of two affected parents should be affected

3. rare recessive trait → shows horizontal inheritance pattern

what is the difference btwn a rare recessive trait and a recessive trait in terms of inheritance patterns? explain why

rare recessive traits show horizontal pattenrns of inheritance patterns

recessive traits that are common in the pop can show vertical (if new mates introduced are also homo for it)

how many chromosomes are in the human genome? how many pairs of autosomes and sex chromosomes?

46 chromosomes

22 pairs of autosomes (numbered 1-22, 44 total)

1 pair of sex chromosomes (2 total - the x and y chromosomes respectively)

what is an autosomal trait

trait conferred by a gene residing on a chromosome that is NOT involved in sex determination

what is a sex-linked trait

trait that is conferred by gene residing on a sex chromosome (x or y)

what are humans w 2 x chromosomes called

female

what are humans w one x and one y chromosome called

male

can everyone be carriers for x-linked recessive traits?

no - males only have one copy of the x chromosome so if that one copy has it they have nothing to override that

what is an example of an x-linked recessive trait in humans and what does it look like in the first and second generations

red-green colour blindness

what is an example of an x-linked recessive trait that has historically ran in the british royal family

hemophilia → don’t have proper blood clotting

are males or females more likely to have x-linked recessive traits

males are more likely (they are way more common in males bc would need TWO copies of (normally rare) recessive genes in females for them to have it

what is an example of an x-linked dominant trait

hypophosphatemia

are x-linked dominant traits more common in males or females

females → have 2 x chromosomes so DOUBLE the chance

can there be carriers for x-linked dominant traits? why or why not?

no → if they have the allele for the trait then they just have the trait and :. can’t be carriers

what 3 trends of inheritance patterns are typically seen with x-linked recessive traits

• never pass from male to their male offspring

• female offspring of affected males are always carriers

• ½ of male offspring of female carriers will inherit trait

what 3 trends of inheritance patterns are typically seen with x-linked dominant traits

• trait seen in every generation (no carriers)

• trait never passes from male to their male offspring

• for affected males, 100% of their male offspring will inherit trait

what 2 trends of inheritance patterns are typically seen with y-linked traits

only affects males

no carriers