What is chromatin made up of?
- DNA
- Non-histone proteins
- RNA
- Histones (H1, H2A, H2B, H3, H4)
What are chromosomes made up of?
- Chromatin
Which histones interact directly with DNA?
- H2A, H2B, H3 and H4
Do all histones between species?
- H1 varies
- H3 and H4 are highly conserved
What structure do histones help DNA form?
- Beads on a string
- Nucleosomes
What is the difference between Euchromatin and Heterochromatin?
- E: lightly packed chromatin often under active transcription
- H: tightly packed chromatin so no transcription
How many pairs of chromosomes do humans have?
- 23 pairs
When do chromosomes replicate?
- S phase of the cell cycle
What is the chromosomal basis of sex determination?
- Normal male: 46XY
- Normal female: 46XX
What types of abnormalities can occur in chromosomes?
- Numerical abnormalities
- Structural abnormalities
- Chromosome mutations within one chromosome
- Chromosome mutations with two chromosomes
What types of numerical chromosomal abnormalities are there?
- Polyploidy (eg triploidy, tetraploidy)
- Aneuploidy (an abnormal number that is not a multiple of the haploid number):
~ Monosomy (loss of one chromosome ie one ‘chromosome pair’ exists as a single chromosome)
~ Trisomy (gain of one chromosome ie one ‘chromosome pair’ exists as a triplet)
What types of structural abnormalities are there?
- Are physical changes to one or more of the chromosomes
- Balanced (change does not cause any missing or extra genetic info)
- Unbalanced (change caused missing or extra genetic info)
What you of chromosome mutations within one chromosome are there?
- Deletion (loss of genetic info)
- Duplication (some genetic material is doubled)
- Inversion (no loss of genetic material but is rearranged instead)
- Ring chromosome (loss of telomeres of ends of both arms and formation of a ring)
- Isochromosome (creation of two non-identical chromosomes - one is a combination of the two short arms, the other is a combination of the two long arms)
What types of chromosome mutations of two chromosomes are there?
- Inversion (no loss of genetic material, but rearrangement of genetic material to a non-homologous chromosome)
- Reciprocal translocation (no loss of genetic material, but an exchange of genetic material between non-homologous chromosomes)
- Robertsonian translocation (rearrangement of genetic material between two chromosomes - q-arms (long) of two acrocentric chromosomes combine to form one ‘super-chromosome’ with the loss of both p-arms (short))
How are karyotypes produced?
- ‘cut and paste’ of chromosome pictures into a systematically organised set of metaphase chromosomes organised into pairs
How are chromosomes organised in Karyotyping?
- Chromosome 1 is the largest and chromosome 22 is the smallest
- Chromosomes are numbered and grouped according to their size and the position of their centromere
- The 23rd pair of chromosomes are the sex chromosomes (XX/XY)
What type of reasons may patients be referred for karyotyping?
- Constitutional (congenital) abnormalities
- Acquired abnormalities
What types of congenital chromosomal abnormalities are there that can be tested for by karyotyping?
- Prenatal screening (eg Down’s syndrome, especially in raised maternal age (>35 years); family history of chromosomal abnormality; abnormal ultrasound of foetus)
- Birth defects (malformations; mental retardation)
- Abnormal sexual development (eg Kleinfelter’s syndrome)
- Infertility
- Recurrent foetal loss
Give examples of acquired chromosomal abnormalities that can be tested for by karyotyping
- Leukaemia and related disorders
What is FISH?
- Fluorescent in situ hybridisation
- Technique where single-stranded nucleic acids (usually DNA, less often RNA) are allowed to interact so that complexes, or hybrids, are formed by molecules with sufficiently similar complementary sequences
- Through nucleic acid hybridisation, the degree of sequence identity can be determined, and specific sequences or genes can be detected and located on a give chromosome
