Chromosomes

I.  Introduction

Cytogenetics:  the subdiscipline within genetics that focuses on chromosome variations.

II.  Portrait of a Chromosome
Karyotype--- A chart arranging  chromosome pictures according to their size, grouped by pairs of homologs.
Anatomy of a chromosome
Centromeres are the largest constriction of the chromosome
Telomeres::
Subtelomeres:
The chromosome region next to the telomere consists of 8,000 - 300,000 bases including:
Repeats similar to the telomere sequence
Shorter repeats
Multigene families of genes
(e.g. olfactory receptor genes)
Chromosomes differ in size
Chromosomes carry different genes

III. Visualizing chromosomes
Obtain tissue from person
   Fetal tissue: 
   Adult tissue:

Karyotype
FISH:
Chromosomal shorthand

Cells which contain a normal chromosome constitution are called euploid.

IV.  Chromosome Abnormalities
Polyploidy
Aneuploidy
   monosomy
   trisomy
Deletion
Duplication
Inversion
Translocation
Extra chromosome set
Extra or missing chromosome
   one chromosome absent
   one chromosome extra
Part of a chromosome missing
Part of a chromosome present twice
Segment of chromosome reversed

Polyploidy
Individuals with three copies of each chromosome are triploid.  

Polyploidy accounts for 17% of all spontaneous abortions and 3% of stillbirths/newborn deaths.

Result of:
Two sperm fertilize one egg.
Haploid sperm fertilizes diploid egg.
Aneuploidy
 
Trisomies and Monosomies
One extra or one missing chromosome results in extra or missing copies of all of the genes on that chromosome.

Most trisomies and monosomies produce inviable embryos.
Some fetuses with trisomy of smaller autosomes survive to birth with syndromic conditions:

The frequency of Down syndrome correlates with the age of the mother
Mother’s age      Down syndrome frequency             in newborns
< 29                1/3000
30 ~ 34           1/600
35 ~ 39           1/280
40 ~ 44           1/70
45 ~ 49           1/40
Sex Chromosome Aneuploidy
Turner syndrome

Uniparental disomy
Inheritance of two chromosomes from one parent is called uniparental disomy.

May occur when nondisjunction occurs in both parents (one disomic gamete and one without homolog)

Loss or nondisjunction of one homolog in early embryo followed by reduplication of remaining homolog.