Genetics Lecture 15: Chromosome Aberrations

Question 1

define aneuploidy and its effects

Answer 1

usually deleterious
an increase or decrease in chromosome number by the addition or loss of individual chromosomes
2n+1 = trisomic 2n-1=monosomic

Question 2

why is mammalian sex chromosome aneuploidy less deleterious than autosome aneuploidy

Answer 2

due to X inactivation

Question 3

define euploidy

Answer 3

the normal number of chromosomes in a species ie. a balanced set eg. 2n for diploid, 3n for triploid

Question 4

define polyploidy

Answer 4

the presence of more than two chromosome sets; a change in ploidy level eg. 3n, 4n

Question 5

define chromosome rearrangements

Answer 5

changes in the structure of chromsomes, including duplications, deletions, inversions and translocations

Question 6

whats the outcome for heterozygotes for different types of chromosomal rearrangements

Answer 6

they show unusual genetic pairing structures during meiosis and thus the resulting meiotic products are specific to the type of rearrangement

Question 7

give examples of exceptional progeny

Answer 7

meiotic non disjunction during gamete formation

Question 8

how does meiotic non-disjunction occur?

Answer 8

1st division non disjunction: XX–>XX+0–> XX+XX+0+0

2nd division non disjunction: XX–>X + X –> XX + 0 + X + X

Question 9

how does non disjunction occur in first meiotic division

Answer 9

if spindle fibres from same poles attach to both centromeres from a pair of homologous chroms and results in both homologous chromosomes moving to same pole thus not separating

Question 10

how does non disjunction occur during second meiotic division

Answer 10

spindle fibres from the same pole attach to both centormeres of a pair of sister chroms and instead of segregating ot oppposite poles, the sister chromatids are pulled toward the same pole

Question 11

overall what are the products of meiosis with normal first division and non disjunction second division

Answer 11

2 normal gametes and 2 aneuploid (one cell with n+1, other n-1)

Question 12

overall what are the products of meiosis with non disjunction at both divisions

Answer 12

4 aneuploid gamets (2 n+1 and two n-1

Question 13

how many chromosomal abnormalities are recognized in human pregnancies - give stats

Answer 13

1 per 100,000
7500 chromosome abnormalities in 15000 abortions
550 chromosome abnormalities in 85000 live births

Question 14

give some examples of human aneuploidy: trisomy

Answer 14

Down/Edwards/Patau syndrome: Trisomy 21/18/13 - life span: 40/

Question 15

give some examples of human aneuploidy:monosomy

Answer 15

Turner Syndrome: Monosomy X - 30-40 years

Question 16

give some examples of non-human aneuploidy

Answer 16

Klinefelter syndrome: XXY - Normal XXX/XXY also normal

Question 17

why do some sex chromosome trisomics have a normal lifespan

which type trisomics are these?

Answer 17

trisomics 2n+1
Y has relatively few active genes
dosage compensation of one X in females through X inactivation in early development in non-marsupials mammals

Question 18

what is a genetic mosaic

give example

Answer 18

individual with 2 or more genetically different types of cells
eg. human somatic mosaic is due to aneuploidy XO/XXY
human females can be seen as mosaic for X chrom genes (some cells paternal X is inactivated, other cells maternal X is inactivated

Question 19

what is the single active X principle

Answer 19

In mammals, the genetic inactivation of all X chromosomes except one in each cell lineage, except in the very early embryo.

Question 20

Which is more deleterious, monosomy or trisomy? Do any monosomes survive?

Answer 20

: Monosomy. Only XO. (DOSAGE PROBLEMS MORE SEVERE PERHAPS)
Monosomic chromosome complements are generally deleterious. Monosomics for all human autosomes die in utero. However monosomic suffer additionally from the unexpected expression of recessive alleles carried on the monosomic chromosome.

Question 21

Do any foetuses with autosomal trisomy survive to full term? If so, which chromosome(s) are involved?

Answer 21

Yes - trisomy13, 18, 21.

Question 22

Do any foetuses with additional sex chromosomes survive to full term? If so, which chromosome(s) are involved?

Answer 22

: Yes – XYY, XXY, XXX

Question 23

Which type of translocation is the more deleterious?

Answer 23

Unbalanced

Question 24

What other form of abnormality is seen in live births? What causes this?

Answer 24

Mosaicism

Question 25

what is a genetic mosaic

Answer 25

mosaics are individuals with 2 or more genetically different types of cells eg human somatic moasic is due to aneuploidy XO/XYYcan be explained by postulating an XY zygote in which the Y chromatids fail to disjoin at an early mitoti c division, so both go to one pole. The phenotypic sex of such individuals depends on where the male and female sectors end up in the body.

Question 26

what did Mary Lyon propose

Answer 26

Single Active X principle and Barr body formation

Question 27

what is a Barr body

Answer 27

visualised condensed X chromosome that has been stained in interphase nuclei

Question 28

how many barr bodies do you find in a cell

Answer 28

Number of X - 1

Question 29

why are X chromosome aneuploids not phenotypically normal?

Answer 29

about 10% of X linked genes show variable patterns of inactivation - dosage compensation is not complete so fifteen percent of X linked genes escape transcriptional silencing in X inactivation

Question 30

what effect does sexual trisomy have on males

Answer 30

XYY males are usually fertile, their meioses are of the XY type; the extra Y is not transmitted and their gametes contain either X or Y, never YY/XY

Question 31

give an example of a viable and fertile trisomic - how did it arise

Answer 31

Datura stramonium - progeny arising from non disjunctinon gamete and normal gamete

Question 32

define monoploid

Answer 32

used to distinguish an individual of a species that is not normally haploid

Question 33

why is polyploidy rare in animals

Answer 33

because it interferes with sex determination and usually polyploid animals have unusual reproductive cycles

Question 34

what types of poyploids do you get

Answer 34

allopolyploids | autopolyploids

Question 35

what are autopolyploids - -what is it due to

Answer 35

chromosom set from the SAME species. can be sexual or asexual due to unreduced gametes: non disjunction of the whole parental set go through iterphase and instead of homologous chromosomes all seaparating into 2 cells, they all stay togetrher, just 2n, which fertilise to get a polyploid zygote: 4n

Question 36

give an example of autopolyploids - how do geneticists construct them - how fertile are autopolyploids

Answer 36

triploids: bananas cross 4n with 2n, the 2n and n gametes unite to form a triploid autopolyploids are sterile

Question 37

discuss alloploidy give example of alloploid give events leading up to its polyploidy

Answer 37

polyploidy caused by a hybridisation event eg. wheat:hexaploid wild diploid crossed with another wild diploid --> steriled diploid hybrid --? polyploidization creates fertile tetraploid -->cross that with wild diploid --> create sterile triploid hybrid --> polyploidization creates fertile hexaploid

Question 38

give examples of chromosomal rearrangements and whether theyre balanced or unbalanced

Answer 38

1. INDEL (unbalanced) 2. duplication 3. translocation (reciprocal and non reciprocal)

Question 39

what is a balanced chromosomal rearrangements

Answer 39

one that causes no gain/loss of genetic material (unbalanced causes dosage problems)

Question 40

discuss deletions | what happens to deletions that span a centromere

Answer 40

involve the loss of DNA sequences in a viable deletion heterozygote, gene for gene attraction results in a loop deletions that span a centromere result in an acentric chromosome that will most likely be lost during cell division

Question 41

why does the copy number of specific genes need to be tightly regulated

Answer 41

to ensure that when a gene is expressed, the functional product is produced at the correct level or dosage - this affects resulting phenotype

Question 42

what are the effects of homozygous deletions

Answer 42

often lethal - equivalent to monosomy

Question 43

what is pseudodominance

Answer 43

when genes heterozygous at each locus lose the wildtype, making it potentially lethal again because of gene balance or because it allows the expression of recessive alleles (deleterious alleles) which would have been masked by the wildtype

Question 44

what is a deficiency loop? how is it formed

Answer 44

when an area is missing in a chromosome due to deletion, the gene - for - gene attraction that normally occurs can only happen in a loop way through synapsis

Question 45

how can deletions be recognised

Answer 45

deficiency/deletion loops in meiosis | pseudodominance

Question 46

what is chromosomal duplication. | give example

Answer 46

duplication within one chromosome's section eg. tetrad during Pachytene 1, mispaired during synapsis, results in misalignment of homologous chroms leads to unequal crossing over between chromatids 2 and 3 and results in deficient and duplicated chromosome regions, some functional gametes can be produced by viable duplication heterozygote

Question 47

why can chromosomal duplication be deleterious/beneficial

Answer 47

due to gene imbalance - gene dosage problems | can provide an opportunity for evolutionary divergence eg. polyploids

Question 48

what is tandem duplication

Answer 48

if the duplicated section of chromosomes are adjacent to the original

Question 49

what is displaced duplication

Answer 49

if the duplicated sections are separated by non duplicated regions

Question 50

how does chromosomal duplication affect evoln

Answer 50

duplications provide raw material for evoln by producing new copies of genes that are free to mutate and take on other functions

Question 51

give an example of deleterious chromosomal replication

Answer 51

in embryonic development of Drosophila, results in Drosophila Bar eye muttion

Question 52

what types of chromosomal inversion

Answer 52

paracentric inversion | pericentric inversion

Question 53

what is a pericentric inversion

Answer 53

involves the centromere

Question 54

compare para- and pericentric inversions

Answer 54

Paracentric inversions do not include the centromere and both breaks occur in one arm of the chromosome. Pericentric inversions include the centromere and there is a break point in each arm.

Question 55

what is an inversion loop

Answer 55

when an inverted chromosome loops round to form a pair (due to gene for gene interaction) with the normal chromosome

Question 56

what is a dicentric bridge

Answer 56

occurs in a paracentric inversion, if you get crossovers within the inversion loop, because one of the chromosome arms is linked to 2 centromeres, and in meiosis, the centromeres migrate to opposite poles, so they pull apart, breaking the chromosome

Question 57

what types of translocations are there

Answer 57

reciprocal and non-reciprocal

Question 58

what does Robertsonian Transolcation cause?

Answer 58

5% of Down Syndrome cases

Question 59

`what is Robertsonian translocation

Answer 59

Down Syndrome between 14 (15) and 21: short arm swapped for long arm non reciprocal translocation, 2 chromosomes become 1, causes Familial Down's

Question 60

what chromosome pairs does Robertsonian translocation occur in

Answer 60

13,14,15,21,22 - the five acrocentric chromosome pairs

Question 61

what is a reciprocal translocation

Answer 61

non homologous chromosomes line up in a cross in Pachytene 1 of Prophase 1

Question 62

how can someone be viable after reciprocal translocation has occured

Answer 62

because no information is lost - and the translocation has not altered normal gene function

Question 63

when do problems in reciprocal translocation arise

Answer 63

in meiosis, because the translocation chromosomes are partially homologous to two different chromosomes. eg. during Pachytene 1, a cross-like structure forms to allow synapsis and crossing over, so for that chromosome pair, there is a normal homolgue (N) and a translocated one.

Question 64

how many segregation patterns from reciprocal translocation are possible?

Answer 64

3. alternate, adjacent- 1, adjacent -2 (rare) | alternate gametes are viable gametes

Question 65

why are X chromosome aneuploids not phenotypically normal?

Answer 65

the preponderance of genes that escape X-inactivation are in the short arm, concentrated near the PAR -pseudoautosomal region

Question 66

what two forms can polyploidisation be in?

Answer 66

sexual : unreduced gametes during meiosis | asexual: endoreduplication during zygotic mitosis

Question 67

what chromosome changes exist in evoln

Answer 67

chromosome fusion and inversion in human evoln polyploidy and inversions associated with speciation in plants duplications associated with the origin of gene families

Question 68

discuss human Chrom 2 wrt. evoln

Answer 68

human chrom 2 is much larger - this suggests it was produced from a fusion of 2 human chromosomes, which explains why human N=23 and ape N=24 Human chrom 2 formed from a Robertsonian translocation from 2 acrocentric chroms

Question 69

what is a gene family | give example

Answer 69

A gene family is a set of several similar genes, formed by duplication of a single original gene GENE FAMILY: genes for human haemoglobin subunits; the ten genes are in two clusters on different chromosomes, called the α-globin and β-globin loci.

Question 70

discuss the globin gene faimly

Answer 70

several genes have arisen from a single ancestral precursor duplication of ancestral gene 500MYA mutation resulted in variation of the 2 copies Transposition led to their location on different chroms further duplications and mutations yield a family of related genes (and pseudogenes) which retain much genetic similarity

Question 71

how does chromosomal duplication occur

Answer 71

unequal crossing-over (recombination) between misaligned homologous chromosomes during meiosis . The chance of this event happening is a function of the degree of sharing of repetitive elements between two chromosomes.