Ch 5 - Extensions on Mendel and Linkage Analysis

lethal alleles

• cause death in early development (before organism is able to reproduce)

• alter phenotypic ratios

• can be dominant or recessive

• progeny is 2:1 rather than 3:1

concept of dominance

interaction between alleles at the same locus

incomplete dominance

• heterozygote is an intermediate of its parents

• phenotypic ratio = genotypic ratio

codominance

heterozygote exhibits both phenotypes (ex: blood types)

What do multiple alleles and codominance create?

greater variety in genotypes and phenotypes

What 3 alleles determines blood type?

I^A, I^B, and i, with I being dominant over i and I^A and I^B being codominant

polygenic

multiple genes play a role in a single trait

What are the causes and consequences of small and large structural variants

• possible changes in expression or function

• loss or gain in content

• motility and context

• DNA repair errors

• heritability or diseases

• sequence identity or of variation

What do genes at multiple loci determine?

a single phenotype

epistasis

one gene hides or masks the effect of another gene at a different locus

types of epistasis?

• recessive epistasis

• dominant epistasis

recessive epistasis

the presence of 2 recessive alleles inhibits the expression of an alleles at a different locus

recessive epistasis example

Bombay phenotype (hh) masks I^A and I^B alleles, causing a type O blood type despite having dominant alleles

dominant epistasis

the presences of a single copy of an allele can inhibit the expression of an allele at a different locus

epistatic gene

the gene that does the masking

hypostatic

the gene whose effect is masked

Cystic Fibrosis symptoms

• persistent coughing, wheezing, or pneumonia

• excessive appetite, but poor weight gain

• infertility in 95% of males

• infertility in 20% of females

• 30-45 years life expectancy

the genetics behind CF?

• mutation of the CFTR gene on q arm of chromosome 7

• most common recessive genetic disease in Caucasians

• affects about 30K kids and young adults in the US

• occurs in about 1 of every 3.5K live births in the US

• more than 10 million Americans are unknown, symptomless carriers

CFTR gene

• cystic fibrosis transmembrane conductance regulator

• forms channels that transport chlorine ions through the cell membrane

• chlorine transport controls movement of water into cells and is very important to tissues

• 188,702 nucleotides long

compound heterozygote

someone with a recessive trait with 2 or more different recessive alleles for the trait (ex: someone with CF)

What happens when there is a mutation in the CFTR gene?

• more than 1K known mutations (ex of multiple alleles)

• different allele combinations determine the severity

• causes failed salt transport, which leads to failed movement of water out of cells

• produces abnormally thick, sticky mucus

  • clogs lungs

  • obstructs pancreas

  • blocks bile duct in liver

  • blocks the vas deferens

pleiotropy

a single gene impacts many different characteristics (ex: CFTR gene)

How do we describe how genes are expressed as a phenotype?

• penetrance

• expressivity

penetrance

the percent of individuals with a particular genotype that express the expected phenotype (how many…)

incomplete penetrance

• more common that complete penetrance

• genotype does not always produce the expected phenotype (ratio)

expressivity

the degree to which a character is expressed (to what degree…)

incomplete penetrance and variable expressivity

• alteration or suppression of the effect of a particular gene due to the effect of genes and not environmental factors

• ex: human polydactyly

sex-linked

genes on the X or Y chromosomes

sex-influenced

• genes on autosomes more readily expressed in one sex

• phenotype depends on sex

• ex: beard growth or hair loss

sex-limited

• autosomal genes expressed only in one sex

• ex: rooster feathering

• ex: male prostate or female ovarian cancer (but anyone can be a carrier

genomic imprinting

• autosomal genes whose expression is influenced by the sex of the transmitting parent

• “parent of origin affect”

continuous characteristics

• characteristics that are polygenic and influenced by the environment are multifactorial

• many overlapping phenotypes (“gray shade” of phenotypes)

• phenocopy

linkage

when genes are located close to each other on the same chromosome, segregate as a unit (don’t assort independently), and are inherited together

Do linked genes produce Mendelian ratios?

no because they do not follow laws of segregation or independent assortment

recombinant chromatids

chromosomes that result from crossing over in Prophase I of meiosis, progeny exhibit mixing of maternal and paternal alleles on a single chromosome

cis linkage

alleles of genes on the same chromosome that are both dominant or recessive

trans linkage

alleles of genes on the same chromosome that are a mix of dominant and recessive

completely linked

genes that are on the same chromosome and close enough that recombination does not often occur

How can you check for linkage?

a testcross

In a testcross, what type of alleles will a homozygous recessive parent always produce…

parental (non-recombinant) allele combos

What are the 3 possible outcomes for a testcross testing for linkage?

1. unlinked

2. complete linkage

3. linked with some crossing over

From a testcross results, how can you tell that genes are unlinked?

the progeny produced are

• ½ nonrecombinant

• ½ recombinant

From a testcross results, how can you tell that genes show complete linkage?

only nonrecombinant progeny is produced

From a testcross results, how can you tell that genes are linked with some crossing over?

there’s mostly nonrecombinant progeny produces, with only a small proportion of recombinant progeny

recombination frequency

tells how far apart 2 loci are on a chromosome, the farther apart 2 genes are, the more likely they are to cross over in meiosis

map units/ centiMorgans (cM)

how genetic distance is measured

x cM is equal to….

x% recombination frequency

equation for recombination frequency?

recombinant progeny/ total progeny times 100

Because recombinant frequency is proportional to the distance between genes on a chromosome, what can we use it to do?

we can use it to find the out the order of genes

Because genetic distance is proportional to physical distance, does that mean they’re identical?

no because of fluctuations in recombination frequency and length variation along the chromosome

Why is recombination not the same as crossing over?

• because recombination shows change

• it is specifically crossing over in between alleles

50 cM and above means genes are…

completely unlinked (only 50 because only half of the chromosome crosses over)

1-49 cM means genes are…

linked

0 cM means genes are…

completely linked