6. Chromosomal abberations

Introduction

Introduction

Chromosomal modifications include

– Change in total chromosome number

– Deletion or duplication of genes or segments of chromosome

– Rearrangements of genetic material within or among chromosomes

▪ Changes can result in phenotypic variation and may be lethal.

Variation in Chromosome Number

Aneuploidy - Organism gains/ loses chromosomes and has other than an exact multiple of haploid set eg 45 or 47 (not an exact multiple of 23)

▪ Euploidy - Complete haploid sets of chromosomes are present.

▪ Polyploidy - More than two sets of chromosomes are present

Terminonlogy for variation in chromosome numbers

Aneuploidy 2n plus or minus x chromosomes

Monosomy 2n-1

Disomy 2n

Trisomy 2n+1

Tetrasomy, pentasomy, etc. 2n+2, 2n+3, etc.

Euploidy Multiples of n

diploidy 2n

polyploidy 3n, 4n, 5n, …

triploidy 3n

tetraploidy, pentaploidy, etc. 4n, 5n, etc.

Autoploidy Multiples of the same genome

Alloploidy (amphidiploidy) extra chromosomes coming from another type of organism Multiples of closely related genomes

Nondisjunction

Aneuploidy arises from nondisjunction.

– Paired homologs fail to disjoin and move to opposite poles during meiosis I or II.

– Leads to a variety of conditions in humans and other organisms

▪ Turner syndrome: 45,X ▪ Klinfelter syndrome: 47,XXY

Diagram on slide 6

Monosomy

– Loss of one chromosome (2n – 1) may have severe phenotypic effects.

– Monosomy for X chromosome occurs in humans.

Monosomy for autosomes is not usually tolerated in humans and other animals--better tolerated in plant kingdom

you wont see monosomy for any of the autosomes (they wouldnt result in a live birth)

– Haploinsufficiency: A single copy of the recessive gene is insufficient to provide a life-sustaining function for organism.

TYPE WHAT HE PREFERS NEXT CLASS

Trisomy

(2n + 1 chromosomes)

– Extra chromosome more likely to produce a viable organism than loss of chromosome.

– Addition of large autosome to diploid has severe effects and is usually lethal during development.

Trisomic plants are viable, but their phenotype may be altered.

– Datura (weed)—12 primary trisomic mutations possible

– Oryza sativa (rice)—trisomics for longer chromosomes results in plants growing slower.

▪ Leaf, stems, grain morphology varied

Trisomy 21

Trisomy 21: Down syndrome (47,21+)

– 1/800 live births (4000–5000 births annually)

– 250,000 individuals currently in United States

listed largest to smallest so 21 is a small chromosome

only 3 of the autosomal trisomy can produce a viable offspring

summary of karyotype, has 47 chromosomes the extra chromosome is chromosome 21

Down syndrome has 12 to 14 characteristics; affected individuals express 6 to 8 on average. –

trisomy 21 children and how down syndrome occurs

– Children prone to respiratory disease and heart malformations

Show higher incidence of leukemia (20 times higher)

▪ Death in older individuals often due to Alzheimer disease

Down syndrome most frequently occurs due to nondisjunction of chromosome 21. – 75% occur during meiosis I.

fertilization with normal gamete creates trisomic condition

Ovum i source of trisomy in 95% of cases

As age of childbearing increases risk of (trisomy 21 increases?????) COPY THE REST

DSCR

Down syndrome critical region (DSCR) – Critical region of chromosome 21

– Contains dosage-sensitive genes

—responsible for many of the phenotypes

– Extra copy of DSCR1 associated with decreased risk of some cancers.

DSCR1 gene encodes protein that suppresses vascular endothelial growth factor -> blocks angiogenesis [formation of new blood vessels]

tumour needs a blood supply in order to grow. with inhibition of the growth factor, tumor doesn't get blood supply it needs to grow so thats how it decreases the risk of certain cancers

not the fact that you have the allele its the fact that the individual has 3 copies (dosage-sensitive)

Random error causing down syndrome

Down syndrome caused by random error— nondisjunction of chromosome 21 – Disorder not expected to be inherited – [Some explanation required!]

▪ Familial Down syndrome: occasionally Down syndrome runs in families.

Translocation of bottom part of chromosome 21 onto another chromosome

initial non disjunction random event influenced by age of mother

If a woman has downsyndrome has a child the likelyhood of it being inherited is essentially 50/50

two other human trisomies that are autosomal

Two other autosomal human trisomies survive to term.

– Patau syndrome (47,13+) – Edwards syndrome (47,18+)

However, they manifest severe malformations and early lethality

Usually before they are 3 or 5 years old

just know it results in a live birth but individual has an extremely reduced life expectancy

there is a list of associated conditions but he said hes “not too worried about traits associated with the condition”

polyploidy

Polyploidy: named based on sets of chromosomes found

▪ Polyploidy relatively infrequent in animal species

-Well known in lizards, amphibians, and fish

More common in plant species

Polyploidy originates in two ways:

– Autopolyploidy -Addition of one or more sets of chromosomes identical to haploid complement of same species

Allopolyploidy - Combination of chromosome sets from different species ---consequence of interspecific matings (typically from fairly closesly related organisms)

Autoploidy

Autopolyploidy

– Each additional set of chromosomes is identical to parental species.

– Triploids AAA, tetraploids AAAA, and so on.

– Autotriploids arise due to: Failiure of chromosomes to segregate during meiotic division

could get a gamete that is 2n by failed meiosis and if it is..

autotetraploids and tetraploids

Autotetraploids – Have even number of chromosomes (4n)

Theoretically more likely to be found in nature than autotriploids

▪ Tetraploids ▪ More likely to produce balanced gametes

Arise when chromosomes have replicated an parent cells fail to divide and instead enters interphase: the chromosome number will have duplicated

Tetraploid cells are produced experimentally from diploid cells - By appluing heat or cold shock to diploid cells undergoing meiosis or By applying colchine to somatic cells undergoing mitosis

doubled the number of chromosomes in the cell because the chromosomes have replicated and the cell does not end up dividing

prevents spindle fiber formation?

Diploid —→ tetraploid mitosis…

Diploid (early prophase)——colchicine added—> Late prophase —-colchicine removed—> tetraploid (cell subsequently reenters interphase)

Autopolyploid flowers and fruits

Autopolyploid flowers and fruits'

– Often increase in size

—greater horticultural or commercial value

– Plants are propagated asexually.

– Include: ▪ Potato species ▪ Winesap apples ▪ Commercial bananas ▪ Seedless watermelons ▪ Cultivated tiger lily

Allotetraploid/amphidiploid

Allotetraploid/amphidiploid results from hybridization of two closely related species.

hybrid organism may be sterile

Sterile hybrids can undergo natural or induced chromosomal doubling, producing fertile amphidiploids

▪ Amphidiploid plants can be produced by somatic cell hybridization.

conceptually this is what we are talking about (far more likely that the species will have the same number of chromosomes because they are closely related

don't have homologous chromosomes but if you double them then each would form a homologous pair

Amphidiploid plants

Amphidiploid plants—often found in nature since they can form balanced gametes

▪ Examples of amphidiploidy plants

– Triticum (wheat) exists as 4n = 28 and 6n = 42

Oat and wheat parallel should be 2n=28=4x

pasta is a 2n=28=4x (x is monoploid chromosome number) wheat, 28 is 7 chromosome from one species and one from another, chromosome doubling gave 28 7x4 is 28

bread wheat is 6n (hybridization product of 3 different species)

Chromosome aberrations

– Changes that delete, add, or rearrange substantial portions of one or more chromosomes

– Include: ▪ Deletions ▪ Duplications ▪ Inversions ▪ Translocations

Total amount of genetic information in chromosome can change: ▪ Deletions ▪ Duplications

▪ Genetic material remains the same but is rearranged: ▪ Inversions ▪ Translocations (reciprocal and nonreciprocal)

[Note clarification!!!] If you move from one chromosome to another, total amount doesn't change, but in meiosis different amount of DNA can be distributed to each gamete

Structural changes

Structural changes due to one or more breaks along chromosomal axis, followed by loss or rearrangement

breakages occur spontaneously

Exposure to chemicals or radiation can increase breakages [X-rays]

▪ Alterations in gametes are heritable.

Deletion

Deletion (deficiency) – Portion of chromosome lost due to breaks

Deletion can occur near one end (terminal deletion) or from interior of chromosome (intercalary deletion).

– Small deletions usually have no adverse effect. [Long deletions usually lethal- why?]

Basically creating a hemizygous gene may reveal lethal recessive alleles or other implications

Deletion or compensation loop – Pairing occurs between normal chromosome and chromosome with intercalary deletion.

unpaired region of normal homolog must buckle to compensate for missing segment

Cri du chat

Cri du chat (cry of the cat) – Results from segmental deletion [i.e. very small] of small terminal portion on chromosome 5

– Severity of syndrome varies with length of deletion

different individuals have different amounts deleted 1 in 25000-50000 births

Eerie cry similar to cat’s meowing – Anatomic malformations, including gastrointestinal and cardiac complications

▪ Those affected have abnormal glottis and larynx development and are often mentally retarded. – 1 in 25,000–50,000 live births

Duplications

Duplications – Repeated segment of chromosome

Pairing in heterozygotes produces compensation loop.

Arise through unequal crossing over between synapsed chromosomes during meiosis

Arise through replication error prior to meiosis

Duplication may result in
– Gene redundancy ▪ Multiple copies of genes

– Phenotypic variation ▪ Example: bar-eye phenotype in Drosophila

– Genetic variability during evolution