Chromosome abnormalities

Question 1

The human genome

Answer 1

The entire sequence of DNA found in every cell of the human body, including the mitochondrial genome.

• ~3,200 million base pairs long
• 22 autosome pairs
• 2 sex chromosomes (X and Y)

Question 2

Chromosome

Answer 2

A single molecule of DNA, composed of two sister chromatids joined at the centromere, each with a long arm (q) and a short arm (p), capped by telomeres.

Question 3

Gene

Answer 3

A specific sequence of DNA containing genetic information.

Question 4

Light bands

Answer 4

• replicate early in S phase
• less condensed chromatin
• transcriptionally active
• gene and GC rich

Question 5

Structure of chromatin

Answer 5

The DNA double helix closely associates with octamers of histone proteins, forming nucleosomes. These coil and condense to form a 30nm chromatin fibre, which condenses further to form chromosomes.

Question 6

Dark bands

Answer 6

• replicate late
• contain condensed chromatin
• AT rich

Question 7

Examination of chromosomes

Answer 7

• karyotyping; uses a light microscope to photograph and arrange chromosomes into pairs using size and banding patterns
• fluorescent in-situ hybridisation (FISH); looks at smaller, targeted areas of a chromosome in higher resolution
• array CGH (comparative genome hybridisation); uses normal reference DNA to determine the number of copies of a specific sequence on a chromosome

Question 8

Types of chromosome abnormalities

Answer 8

Abnormalities may relate to chromosome number or structure. They may be constitutional (all cells) or somatic (certain cells/tissues).

Question 9

Abnormalities of chromosome number

Answer 9

• aneuploidy; single chromosome number eg. trisomy, monosomy
• polyploidy; overall chromosome number eg. triploidy, tetraploidy

These occur due to errors in cell division, such as non-disjunction in which paired chromosomes do not separate.

Question 10

Aneuploidy

Answer 10

An abnormality in chromosome number in which an individual has one (monosomy) or three (trisomy) copies of a particular chromosome. Autosomal abnormalities are more serious than those in sex chromosomes, and are often incompatible with life. The risk of trisomy increases with increasing maternal age, due to a lengthier interval between the onset and completion of oocyte meiosis during which damage can occur.

Question 11

Common chromosome number abnormalities

Answer 11

• Down syndrome; trisomy 21 (XX, 47, +21)
• Edwards syndrome; trisomy 18 (XX, 47, +18)
• Patau syndrome; trisomy 13 (XX, 47, +13)
• Turner syndrome; (45, X)
• Klinefelter syndrome; (47, XXY)
• Triploidy; (69)

Question 12

Down syndrome

Answer 12

Trisomy 21 may result from non-disjunction during meiosis (95%), Robertsonian translocation (4%) or non-disjunction after fertilisation, resulting in mosaicism (1%). Affected individuals have distinct facial features and a single palmar crease. Newborns often exhibit neonatal hypotonia. Adults are at higher risk of Alzheimer’s disease.

Question 13

Edwards syndrome

Answer 13

Caused by trisomy 18. Affected individuals may suffer from multiple malformations, especially of the heart and kidneys. A common sign in newborns is flexed fingers.

Question 14

Patau syndrome

Answer 14

Caused by trisomy 13. Affected individuals may suffer from multiple malformations, including incomplete lobation of the brain, cleft lip and congenital heart disease.

Question 15

Klinefelter syndrome

Answer 15

Caused by the karyotype (47, XXY). Affected individuals are males with a tall stature and poorly developed secondary sex characteristics. They are infertile.

Question 16

Turner syndrome

Answer 16

Caused by the karyotype (45, X). Affected individuals are females with a short stature and poorly developed secondary sex characteristics. They are infertile.

Question 17

Abnormalities of chromosome structure

Answer 17

• translocations (reciprocal/Robertsonian)
• deletion
• duplication
• inversion
• ring chromosome
• marker chromosome
• complex rearrangements

Question 18

Robertsonian translocation

Answer 18

Where two acrocentric chromosomes break at/close to their centromeres. The long arms fuse while the short arms are lost, resulting in the formation of a new translocated chromosome.

Question 19

Balanced translocation

Answer 19

Where translocated chromosomes possess the same genetic material, just in different positions, and so have no effect on the phenotype. Predisposes to unbalanced translocation.

Question 20

Unbalanced translocation

Answer 20

Where translocated chromosomes result in aneuploidy. In reciprocal translocation, this may be partial trisomy/monosomy.

Question 21

Reciprocal translocation

Answer 21

Where any two non-homologous chromosomes break and exchange fragments, forming two new translocated chromosomes.

Question 22

Larger deletions/duplications

Answer 22

Mispairing at repeated sequences can cause unequal crossing over of chromosomes in meiosis, resulting in chromosome abnormalities affecting many genes.

Question 23

Mosaicism

Answer 23

An individual possesses two populations of cells with different genetic constitutions, usually as a result of an error in mitosis. Occurs after fertilisation, and may be somatic or gonadal.