genetics unit 2

many diseases and birth defects are a direct result of missing, broken or extra chromosomes

Down syndrome, cri-du-chat syndrome, patau syndrome

euploidy

involves changes to the number of haploid chromosome sets

aneuploidy

gain or loss of one or more chromosomes but not complete sets

monosomy

only one member of a homologous pair; partner is missing

trisomy

three homologs for a particular chromosome a

a=telomere

b= short arm (p)

c=centromere

d=long arm (q)

e=chromatid

Aneuploidy definition for policy numbers

monosomy = 2n-1

disomy = 2n

trisomy = 2n+1

tetrasomy, pentasomy = 2n +2 or 2n+3…. etc

euploidy definitions of ploidy

diploidy =2n

polyploidy= 3n, 4n , 5n

triploidy = 3n

autopolyploidy

euploidy, multiples of the same genome

allopolyploidy

• amphidiploidy

• multiples of closely related genomes

• falls into euploid categories

trisomy 21 Down syndrome phenotype

• growth failure/mental retardation

• flat head

• abnormal ears

• loops on finger and palm crease

• unilateral or bilateral absence of one rib

• intestinal blockage

• umbilical hernia

• abnormal pelvis

• diminished muscle tone

• enlarged colon

• congenital heart disease

Down syndrome probability

• occurs with with women’s age

• father does not effect

• there is a pause in crossing over in meiosis

• nondisjunction is the mutation

who produces the most offspring with down syndrome?

• younger mothers due to those being the most likely to reproduce

• risk is higher with age, however, reproduction is less common

if nondisjunction happens in meiosis 1 vs 2

• in meiosis 1, there is 2 trisomic and 2 monosomic

• in meiosis 2, there’s 2 disomic, one trisomic and one monosomic gamete.

in most Down syndrome cases where does nondisjunction occur?

meiosis 1

patau syndrome

• extra copy of 13

• death within a year

• 1/20,000 births

• likely so severe that it occurs in miscarriage

• in 1/100 miscarriages

• 30% of abortions

edwards syndrome

extra copy in 18

• results in miscarriage often

• fatal within first year

monosomy

• occurs due to nondisjunction

• we often never see this due to its lethal effects before birth.

• not characterized by syndromes

• haploid at that chromosome

• for every monosomy, every recessive allele is unmasked

mutations that are structural

• deletions

• duplications

• inversions

• translocations

cri du chat

• deletion at chromosome 5

• 1/50,000 births

• mental retardation

• slow motor skill development

• low birth weight and slow growth

• small head (microcephaly_

• partial toe and finger webbing

• wide set eyes

• high pitched cries

hypertelorism

wide set eyes

how can chromosomes break and rejoin?

• spontaneous

• ionizing radiation

• chemical insult

• break points of chromosomes are highly reactive “sticky” whereas normal ends of chromosomes are capped by telomeres, which do not readily bond to other molecules

ionizing radiation

• production of free radicals that act like little atomic cannon balls blasting through strands of DNA or chromosomes

unequal crossing over results in both

duplication and deletion

bar eye in drosophila

is a genetic mutation that causes a reduction in the size of the Drosophila eye, leading to a characteristic bar shape.

duplications as a source of evolutionary novelty

gene families

• globins (alpha and beta in mammals)

• ribosomal DNA

• homeobox genes

subfunctionalization of genes

is a process in which gene duplicates evolve to partition the ancestral functions between them, each taking over part of the original gene's role.

neofunctionalization

is a process by which duplicated genes evolve new functions that are distinct from their original roles, contributing to functional diversity in an organism.

duplications as a source of evolutionary novelty (goblin)

in the beta goblin gene family e is expressed in early embryo, Gy and Ay whose proteins differ by just one amino acids in the fetus and sigma and betta in the adult. the different biochemical properties of the resulting global proteins are thought to reflect slight changes in the physiological role that hemoglobin plays during the course of human development.

heterozygosity for inversions suppresses recombination

• organisms heterozygous for an inversion tend to undergo little crossing over in the inverted region

• can be the cause of low fertility

if there is crossing over with inversions

• the two chromatids produced from the crossing over event will produce non-viable gametes

• however the two chromatids produced from non crossover chromatids will produce viable gametes

inversion of genes

is a chromosomal mutation where a segment of DNA is reversed within the chromosome, potentially affecting gene expression and function.

what happens if a loci inside an inversion affects a single trait or suite of related traits

they will be inherited together and allele combinations will not be broken up by recombination

a suite of tightly linked loci that affect a single trait is collectively called

a supergene

examples of inversions and evolution

mimicry coloration in some species of butterflies,

snail shell color pattern in some species

translocation of a gene

possible origin of a reciprocal translocation between two nonhomologous chromosomes

this photo shows

synapsis of translocation heterozygote

what does this image show?

the two possible segregation patterns leading to gamete formation

familial down syndrome

• refers to cases where Down syndrome is inherited due to a parental translocation, specifically where a piece of chromosome 21 attaches to another chromosome.

• normal ploidy, but the fused extra piece causes down syndrome

this photo describes what kind of ploidy

triploidy

what is indicated as the origin of a liveborn human triploid and how many chromosomes

• diplospermy II

• suggested from literature that 46 chromosomes were of paternal origin

• results in 69 chromosomes

plants and polyploidy

• more than 70% of flowering plants are of polyploid origin

• in many genera, different species will have different ploidy levels (multiple of a base number) representing a series of polyploids

example of plants and polyploidy

• in genus chrysanthemum different species have chromosome numbers of 2n=18, 36, 54,72,90 and 198

• all multiples of a base chromosome number of 9

label left and right

left: autopolyploidy

right: allopolyploidy

examples of autopolyploids

• Winesap apples

• commercial bananas

• seedless watermelons

• cultivated tiger lily

Give overview example of autopolyplooidy with 2n=6 parent species

• meiotic error creates two gametes with 6 unreduced chromosomes each

• self fertilization produced a zygote thats 4n=12 aka tetrapolyploidy

offspring with polyploid karyotypes may be

viable and self fertile

some examples of allopolyploids

• bread wheat

• oats

• cotton

• strawberries

• coffee

• xenopus frogs

• unisexual whiptail lizards

give an overview of allopolyploidy

• diff diploid number in each parent

• Meiotic error in one parent does not reduce its diploid number

• Creates hybrid with odd number

• One unreduced gamete will cross over with reduced gamete

• Creates viable fertile hybrid

sutton and boveri united the fields of cytology and genetics - describe what Sutton stated

1903 that there are more unit factors than chromosomes

certain genes segregative as if they were linked and are part of the same chromosome thus they are inherited as

single unit

during prophase I of meiosis, synapsed chromosomes reciprocally exchange segments which reshuffles alleles between homologs - this frequency of crossing over is proportional to

the distance between them

Formation of autotetraploids experimentally

• colchine inhibits spindle formation (prohpase)

• Can be used to generate 4n

• Cold or heat shock can accomplish the same thing

Formation of allopolyploids creates what level of fertility

• generally infertile unless chromosome doubling occurs

Fragile X syndrome overview

• most common kind of inherited mental retardation

• Named for fragile site

• Caused by expansion of 3-base pair repeat CGG in a gene near the tip of the long arm of X chromosome

• More common in males

fragile x mutation

normal range:7-60 repeat w average 30

Pre mutation: 60-230 repeats

• pre mutation is unstable: maternally inherited pre mutation with greater than a hundred repeats always expands to full

Full mutation is beyond 230 to the 1000s of repeats

What happens in full mutation of fragile x mutation

dna becomes abnormally methylated, promoter is inactivated and gene is silenced

Huntington disease

• autosomal dominant lethal (chrom. 4)

• Progressive neurological deterioration

• First symptoms after repo age

• 1/8 known neurodegenerative diseases caused by expansion of CAG repeats

• All show inverse correlation with age of onset and number of repeats

Genes ____ if they are on different chromosomes but show linkage if they are on the same chromosome

Assort independently

Independent assortment

• two pairs of chromosomes

• Four genetically different gametes

• Each containing different combinations of alleles

• Formed in equal proportions

If genes are linked on the same chromosome, if not crossing over occurs what is produced

• only two genetically different gametes are produced

• Complete linkage produces only parent gametes, in equal proportions

Crossing over between two linked genes involves what and generates what

• involves two nonsister chromatids

• Generates two new allele combinations called recombinant or crossover gametes

When the loci of the two linked genes are far apart…. What does crossing over look like?

it is very frequent

If there is always one cross over… what do gametes look like

• 50% of gametes will be parental

• 50% will be recombination

If the loci of two linked genes are closer together crossing over is less frequent… however if it does occur what does that look like?

• less than 50% will be recombination

• Greater than 50% will be parental

Complete linkage gives a 1:2:1 phenotypic ratio in the f2 generation… what about a test cross?

1:1

Studies with drosophila show that synapsed chromosomes in meiosis wrap around each other to create ____ x shaped intersections, which are points of genetic exchange

chiasmata

Linked genes exist in a linear order along the chromosome and the amount of crossing over is proportional to the ______ between gene loci on the chromosome

distance

Why are two genes located relatively close to each other along a chromosome less likely to cross over?

less likely to have a chiasma form between them

This shows what

the distance that is required for a mutation

The percentage of offspring resulting from recombinant gametes depends on what

distance between two genes on the chromosome

Mapping distance for crossing over

• the frequency of exchange is an estimate of the relative distance between two genes along the chromosome

• One map unit (mu) is defined as 1% recombination between two genes on a chromosome

A single crossover

the further apart two loci are on a chromosome the more likely a random crossover will occur

If the mapping of the distance is 30 mu how many gametes are affected

30% will be recombinant

And the meiotic crossing over is 60%

a single crossover between two non sister chromatids involves what?

two of four chromatids and produces 2 recombinant and two parental gametes

if a crossover occurs between two genes in a single meiosis

half of the gametes produced from that meiosis will be recombinant

the percentage of meioses in which a crossover occurs between two genes is (SCO)

twice the percentage of recombinant gametes produced

in single crossover when two genes are more than 50 map units apart a crossover can be expected to occur between them in what percent of meioses?

100 percent

double crossover

where do the non crossover phenotypes occur in the greatest proportion?

F2 offspring

where do double crossover phenotypes occur in

the smallest proportion

the distance between two genes in a three point cross is equal to the

percentage of all detectable exchanges occurring between them

*includes all single and double crossovers

how do you determine order from a three point cross?

• first determine arrangement of alleles on the homologs of the heterozygote yielding the gametes by locating the reciprocal non crossover phenotypes

• then test cross each three possible orders to determine which yields observed double crossover phenotype

• the one that does is the correct order

Genes K and D are 6 map units apart. What does that mean?

that recombination occurs 12% of the time between these genes

Genes L and M are 10 map units apart. You cross a homozygous LLMM with an llmm, and then testcross the F1. If there are 100 offspring, how many are Llmm?

5

Three genes on the Drosophila X chromosome are examined pairwise. It is determined that they have the following recombination rates:
(1) yellow, white 0.5 percent
(2) white, miniature 34.5 percent 
(3) yellow, miniature 35.4 percent 
Which two genes are physically closest together?

yellow and white

Two genes that are 60 map units apart are expected to show _____.

independent assortment

the three basic criteria for autosomal mapping

• one parent must be heterozygous for all traits studied

• the triple heterozygote must be crossed to individual with recessive phenotype for all traits (test cross)

• the genotypes must be apparent from the phenotype and a large sample size is needed

why are two point crosses between distant genes inaccurate

• the expected frequency of multiple exchanges between two hemes can be predicted from the distance between them

• the farther apart two genes are the greater the probability multiple crossovers will occur

  • degree of inaccuracy increases as the distance between them does

  • most accurate maps are constructed from closely linked genes

inference (I)

reduces the expected number of multiple crossovers when a crossover event in one region of the chromosome inhibits a second event nearby

Interference is positive if

fewer double crossover events than expected occur in a given region

Inference is negative if

more double crossover events than expected occur

When two genes are close together what happens with interference

• positive

• Accuracy of mapping is high

As distance between genes increases…

• interference decreases

• Multiple crossing over is more likely

• The accuracy of mapping decreases

How do we quantify the disparities that result from interference

• the coefficient of coincidence (C) is calculated

What is the coefficient of coincidence

• the observed number of DCO divided by the expected number of DCOs

Interference can be quantified by

i= 1- C

How do we determine expected number of double crossover events?

• assuming independence in two regions the expected probability of double crossovers is the probability of recombination in one region times the probability of recombination in other

The phenotypic offspring representing double crossovers______

occur less frequently than single-crossover class