Genetics Lecture 15: Chromosome Aberrations Flashcards
define aneuploidy and its effects
usually deleterious
an increase or decrease in chromosome number by the addition or loss of individual chromosomes
2n+1 = trisomic 2n-1=monosomic
why is mammalian sex chromosome aneuploidy less deleterious than autosome aneuploidy
due to X inactivation
define euploidy
the normal number of chromosomes in a species ie. a balanced set eg. 2n for diploid, 3n for triploid
define polyploidy
the presence of more than two chromosome sets; a change in ploidy level eg. 3n, 4n
define chromosome rearrangements
changes in the structure of chromsomes, including duplications, deletions, inversions and translocations
whats the outcome for heterozygotes for different types of chromosomal rearrangements
they show unusual genetic pairing structures during meiosis and thus the resulting meiotic products are specific to the type of rearrangement
give examples of exceptional progeny
meiotic non disjunction during gamete formation
how does meiotic non-disjunction occur?
1st division non disjunction: XX–>XX+0–> XX+XX+0+0
2nd division non disjunction: XX–>X + X –> XX + 0 + X + X
how does non disjunction occur in first meiotic division
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
how does non disjunction occur during second meiotic division
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
overall what are the products of meiosis with normal first division and non disjunction second division
2 normal gametes and 2 aneuploid (one cell with n+1, other n-1)
overall what are the products of meiosis with non disjunction at both divisions
4 aneuploid gamets (2 n+1 and two n-1
how many chromosomal abnormalities are recognized in human pregnancies - give stats
1 per 100,000
7500 chromosome abnormalities in 15000 abortions
550 chromosome abnormalities in 85000 live births
give some examples of human aneuploidy: trisomy
Down/Edwards/Patau syndrome: Trisomy 21/18/13 - life span: 40/
give some examples of human aneuploidy:monosomy
Turner Syndrome: Monosomy X - 30-40 years
give some examples of non-human aneuploidy
Klinefelter syndrome: XXY - Normal XXX/XXY also normal
why do some sex chromosome trisomics have a normal lifespan
which type trisomics are these?
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
what is a genetic mosaic
give example
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
what is the single active X principle
In mammals, the genetic inactivation of all X chromosomes except one in each cell lineage, except in the very early embryo.
Which is more deleterious, monosomy or trisomy? Do any monosomes survive?
: 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.
Do any foetuses with autosomal trisomy survive to full term? If so, which chromosome(s) are involved?
Yes - trisomy13, 18, 21.
Do any foetuses with additional sex chromosomes survive to full term? If so, which chromosome(s) are involved?
: Yes – XYY, XXY, XXX
Which type of translocation is the more deleterious?
Unbalanced
What other form of abnormality is seen in live births? What causes this?
Mosaicism
what is a genetic mosaic
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.
what did Mary Lyon propose
Single Active X principle and Barr body formation
what is a Barr body
visualised condensed X chromosome that has been stained in interphase nuclei
how many barr bodies do you find in a cell
Number of X - 1
why are X chromosome aneuploids not phenotypically normal?
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
what effect does sexual trisomy have on males
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
give an example of a viable and fertile trisomic - how did it arise
Datura stramonium - progeny arising from non disjunctinon gamete and normal gamete
define monoploid
used to distinguish an individual of a species that is not normally haploid
why is polyploidy rare in animals
because it interferes with sex determination and usually polyploid animals have unusual reproductive cycles
what types of poyploids do you get
allopolyploids
autopolyploids
what are autopolyploids - -what is it due to
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
give an example of autopolyploids - how do geneticists construct them - how fertile are autopolyploids
triploids: bananas
cross 4n with 2n, the 2n and n gametes unite to form a triploid
autopolyploids are sterile
discuss alloploidy
give example of alloploid
give events leading up to its polyploidy
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
give examples of chromosomal rearrangements and whether theyre balanced or unbalanced
- INDEL (unbalanced)
- duplication
- translocation (reciprocal and non reciprocal)
what is a balanced chromosomal rearrangements
one that causes no gain/loss of genetic material (unbalanced causes dosage problems)
discuss deletions
what happens to deletions that span a centromere
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
why does the copy number of specific genes need to be tightly regulated
to ensure that when a gene is expressed, the functional product is produced at the correct level or dosage - this affects resulting phenotype
what are the effects of homozygous deletions
often lethal - equivalent to monosomy
what is pseudodominance
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
what is a deficiency loop? how is it formed
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
how can deletions be recognised
deficiency/deletion loops in meiosis
pseudodominance
what is chromosomal duplication.
give example
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
why can chromosomal duplication be deleterious/beneficial
due to gene imbalance - gene dosage problems
can provide an opportunity for evolutionary divergence eg. polyploids
what is tandem duplication
if the duplicated section of chromosomes are adjacent to the original
what is displaced duplication
if the duplicated sections are separated by non duplicated regions
how does chromosomal duplication affect evoln
duplications provide raw material for evoln by producing new copies of genes that are free to mutate and take on other functions
give an example of deleterious chromosomal replication
in embryonic development of Drosophila, results in Drosophila Bar eye muttion
what types of chromosomal inversion
paracentric inversion
pericentric inversion
what is a pericentric inversion
involves the centromere
compare para- and pericentric inversions
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.
what is an inversion loop
when an inverted chromosome loops round to form a pair (due to gene for gene interaction) with the normal chromosome
what is a dicentric bridge
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
what types of translocations are there
reciprocal and non-reciprocal
what does Robertsonian Transolcation cause?
5% of Down Syndrome cases
`what is Robertsonian translocation
Down Syndrome between 14 (15) and 21: short arm swapped for long arm
non reciprocal translocation, 2 chromosomes become 1, causes Familial Down’s
what chromosome pairs does Robertsonian translocation occur in
13,14,15,21,22 - the five acrocentric chromosome pairs
what is a reciprocal translocation
non homologous chromosomes line up in a cross in Pachytene 1 of Prophase 1
how can someone be viable after reciprocal translocation has occured
because no information is lost - and the translocation has not altered normal gene function
when do problems in reciprocal translocation arise
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.
how many segregation patterns from reciprocal translocation are possible?
- alternate, adjacent- 1, adjacent -2 (rare)
alternate gametes are viable gametes
why are X chromosome aneuploids not phenotypically normal?
the preponderance of genes that escape X-inactivation are in the short arm, concentrated near the PAR -pseudoautosomal region
what two forms can polyploidisation be in?
sexual : unreduced gametes during meiosis
asexual: endoreduplication during zygotic mitosis
what chromosome changes exist in evoln
chromosome fusion and inversion in human evoln
polyploidy and inversions associated with speciation in plants
duplications associated with the origin of gene families
discuss human Chrom 2 wrt. evoln
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
what is a gene family
give example
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.
discuss the globin gene faimly
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
how does chromosomal duplication occur
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.
