Chromosome Mutations

Flashcards on Chromosome Mutations

centromere

Chromosomes can be classified based on __ position

Chromosome Nomenclature

The scientific naming system for chromosomes.

inv

inversion

mat

Maternal

pat

Paternal

p

Short arm of the chromosome

q

Long arm of the chromosome

r

Ring chromosome

s

Satellite

t

Translocation

46, XY

Normal male

46, XX

Normal female

45, X0

Turner syndrome

47, XXX

Triple X

47, XXY

Kleinfelter syndrome

47, XYY

Jacobs syndrome

46, XX+21

Female – trisomy 21

46, XY del (q7)

Male – deletion in long arm

46, XY t (7;9)

Male – translocation between chromosomes 7 & 9

Mutation

Any spontaneous or inducible changes in the structure of the DNA or a process by which a gene undergoes a structural change.

Mutagens

The physical or chemical agents that cause the mutation

Mutagenesis

Process by which a gene undergoes a structural change.

Somatic mutations

Mutations in somatic cells (body cells)

Germline mutations

Mutations in germ cells

Gene mutations

Mutations that appear in the base sequence of DNA

Mutations at the chromosome level

Changes in the number and structure of chromosomes

Three major groups of mutations

Chromosome number mutations, Chromosome structure mutations, DNA mutations

Chromosome number mutations classified in 3 major groups

Euploidy, Aneuploidy, Uniparental Disomy

Euploidy

An increase or a decrease of the number of chromosomes with respect to fold change of "n"

Diploidy

Normal human karyotype, 2n = 46

Triploidy

3n = 69

Tetraploidy

4n = 92

Types of euploidy

Monoploidy, Polyploidy, Mosaicism, Chimerism

Monoploidy

Presence of chromosomes in the individual's body cells as much as (n) in gamete cells.

Polyploidy

Increase within the number of chromosomes in fold change of n.

Mosaicism

Caused by the errors in mitosis after zygote formation

Chimerism

Individual's body cells contain different numbers of chromosomes; cells have the same chromosome numbers, but are produced by two different zygotes.

Transplantation-based chimerism

After transplantation, carries the DNA of the donor.

Congenital chimerism

Two zygotes just fuse to each other but the resulting individual is single so different tissues have different DNA profiles

Micro-chimerism

stem cells may translocate to maternal circulatory system and behave as they belong to baby, thus, some tissues may have mosaic karyotypes such as 46, XY and 46, XX

Aneuploidy

Changes in the number of chromosomes are not fold-change of n but more or less than n.

Trisomy

2n + 1

Tetrazomy

2n + 2

Monosomy

2n-1

Two mechanisms of Aneuploidy

Chromosomal non-disjunction, Anaphase Lag

Chromosomal non-disjunction

While the chromosomes or chromatids are to be separated from each other moving apart to opposite poles some of them may move to the same pole without any separation.

Anaphase Lag

As chromatids leave their centromeres and go to opposite poles, one is left behind in anaphase.

Trisomy

A chromosome set of 2n+1=47 instead of normal set of 2n=46.

Patau Syndrome

Trisomy 13

Edward’s Syndrome

Trisomy 18

Down Syndrome

Trisomy 21

Tetrasomy

Either there are four of certain homologous chromosome pairs instead of two (Ex: 48, XXXX) Or there are trisomies of two separate homologous chromosome pairs. (Ex: 48, XX, +1; +14).

Monosomy

Lack of diploid chromosome number.

Turner Syndrome (45, X0)

Example of Monosomy

Isodisomy

Both chromosome sets come from father's one of the two chromosome set.

Heterodisomy

Both chromosome sets come from father's chromosome set

Structural changes

Breaks in chromosomes and, accordingly, rearrangements in chromosomes.

Balanced mutations

No change in chromosome number and gene content due to breaks and rearrangements

Imbalanced mutation

Loss of genomic DNA

Chromosome Structure Mutation types

Translocations, Deletions, Duplications, Inversions, Ring chromosome ,Dicentric chromosome

Translocation

Replacement of a piece that breaks off from one chromosome and integrates into another chromosome.

Types of translocations

Reciprocal translocation, Centromeric fusion (Robertsonian), Transposition (insertional translocation)

Reciprocal translocation

Two non-homologous chromosomes break and broken parts are exchanged.

Reciprocal translocation example

ABL gene from chromosome 9 joins to the BCR gene on chromosome 22, to form the BCR-ABL fusion gene.

Centromeric fusion (Robertsonian)

Special type of translocation observed in acrocentric chromosomes.

Centromeric fusion (Robertsonian)

Long (long-long) and short arms (short- short) of the two chromosomes join together and translocated chromosomes are formed.

Transposition (insertional translocation)

One of the two non-homologous chromosomes breaks at two points and the other at one point.The part between the two breaks goes to fuse with the other non-homologous chromosome.

Deletions

Removal of a piece from the chromosome.

Duplications

Occurs as a result of transposition between homologous chromosomes.

Inversions

Change that occurs on a single chromosome; there are two breaks in one chromosome.

Pericentric inversion

Break is formed on the long(q) and short(p) arms of the chromosome, and the part between it contains a centromer.

Paracentric inversion

Has two breaks in one arm of the chromosome.

Ring Chromosome

Breaks form on both ends of a chromosome, and the broken ends stick together, and as a result, a ring-shaped chromosome is formed, the broken parts just disappear.

Dicentric Chromosome

A two centromeric chromosome consisting of two chromosome parts with a centromere, losing their broken ends without centromere and joining them.