Lesson 4:Mutation (IV)

Chromosomal Mutation

There are 2 types of chromosome mutation:

1. Change in chromosome number
2. Change in chromosome structure  

(a) Change in chromosome number

These are usually caused by non-disjunction occurring during meiosis but they can also occur during mitosis.

There are 2 types: 

Aneuploidy

• It is a condition of a nucleus, cell or organism in which one or more chromosomes have been added to or deleted from the complete set such that total no. of chromosome in not exact multiple of the haploid number 
• Aneuploids are diploid cells or organisms that have lost or gained 1 or more chromosomes. 
• Monosomy is the condition of diploid cells or organisms lacking in a single chromosome  
• Example: Turner syndrome( 45, XO) 
• Trisomy is the condition of diploid cells or organisms with an additional chromosome( 2n+1). 
• Example: Trisomy 21 (down syndrome) and Klinefelter syndrome (47, XXY) 
• Disjunction is the separation of homologous chromosomes or sister chromatids in anaphase to opposite poles of a dividing cell. 
• Non- disjunction is the failure of a pair or pairs of homologous chromosomes to separate and move to opposite poles of the cell  
• Happen during: 

                      Anaphase I meiosis  --homologous chromosome fail to separate normally

                      Anaphase II meiosis   -- sister chromatids fail to separate  normally

• Mitosis –where sister chromatids fail to separate 
• As a result of non-disjunction, one gamete receives two copies of the gene while the other gamete receives none. In the next step, the faulty gametes engage in fertilization, the offspring will have an incorrect chromosome number. This is called aneuploidy.
 

Down syndrome

• Down syndrome or trisomy 21 is a chromosomal disorder caused by the presence of an extra 21st chromosome.
• Individuals with Down’s syndrome have three instead of the normal 2 chromosomes 21.
• This occurs when a mutant gamete that has 2 chromosomes 21 fertilises a normal gamete with one chromosome 21.
• Mutant gamete with 2 chromosome 21 can be produced by:

                  *  Non-disjunction of homologous chromosome pair 21 
                      occurs during anaphase I of meiosis

                  * Non-disjunction of sister chromatids of chromosome 21
                     occurs during anaphase II of meiosis 

• Individuals with Down syndrome tend to have a lower than average cognitive ability, often ranging from mild to moderate learning disabilities. 

Klinefelter's syndrome

• Occurs when a male inherits more than one X chromosome producing genotypes such as 47+ XXY( XXY, XXYY, XXXY)
• Caused by non-disjunction of sex chromosome during meiosis
• Affected males have an extra X sex chromosome. The principal effects are development of small testicles and reduced fertility. 
• Because of the extra chromosome, individuals with the condition are usually referred to as "XXY Males", or "47, XXY Males".   
• Affected males are almost always effectively sterile, although advanced reproductive assistance is sometimes possible. 
• Some degree of language learning impairment may be present, and neuropsychological testing often exhibit deficits in executive functions. 
• In adults, possible characteristics vary widely and include little to no signs of affectedness, a lanky (thin & tall person), youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue). 
• Gynecomastia is present to some extent in about a third of affected individuals, a slightly higher percentage than in the XY population, but only about 10% of XXY males' gynecomastia is noticeable enough to require surgery.

Turner syndrome

• An example of monosomy in the human population. Female individuals have only 45 chromosomes (45,X).It is caused by the absence of a second X chromosomes. Non-disjunction of sex chromosomes occur during anaphase.
• In females, non-disjunction produces gametes with XX chromosomes or no sex chromosomes. In males, this produces gametes with XY chromosomes or no sex chromosomes. When a gamete a normal X chromosomes fuses with a gamete without X chromosomes, the zygote formed contains monosomy X (XO).