Chromosomes An overview This PowerPoint file contains a number of slides that may be useful for teaching of genetics concepts. You may use these slides and their contents for non-commercial educational purposes.

Chromosomes This presentation includes: The anatomical structure of chromosomes Classification of chromosomal anomalies Description of chromosomal anomalies Examples of chromosomal anomalies Explanation of normal and abnormal karyotypes Chromosomal findings in early miscarriages.

Chromosomes Chromosomes are made of DNA. Gene for cystic fibrosis (chromosome 7) Chromosomes are made of DNA. Each contains genes in a linear order. Human body cells contain 46 chromosomes in 23 pairs – one of each pair inherited from each parent Chromosome pairs 1 – 22 are called autosomes. The 23rd pair are called sex chromosomes: XX is female, XY is male. In the slide you can see chromosomes arranged in pairs, this is called a karyotype (chromsome complement) One of each pair is inherited from the mother, the other from the father Ask participants - what sex is this individual? (Male, XY) Gene for sickle cell disease (chromosome 11)

Chromosomes p Centromere q Chromosome 5

Chromosomes as seen at metaphase during cell division Telomere DNA and protein cap Ensures replication to tip Tether to nuclear membrane Light bands Replicate early in S phase Less condensed chromatin Transcriptionally active Gene and GC rich Short arm p (petit) Centromere Joins sister chromatids Essential for chromosome segregation at cell division 100s of kilobases of repetitive DNA: some non-specific, some chromosome specific Long arm q Dark (G) bands Replicate late Contain condensed chromatin AT rich Telomere

Human chromosome banding patterns seen on light microscopy Different chromosome banding resolutions can resolve bands, sub-bands and sub-sub-bands

A pair of homologous chromosomes (number 1) as seen at metaphase Locus (position of a gene or DNA marker) Allele (alternative form of a gene/marker)

Total Genes On Chromosome: 723 373 genes in region marked red, 20 are shown FZD2 AKAP10 ITGB4 KRTHA8 Genes are arranged in linear order on chromosomes WD1 SOST MPP3 MLLT6 STAT3 BRCA1 breast cancer 1, early onset GFAP NRXN4 NSF NGFR CACNB1 HOXB9 HTLVR ABCA5 CDC6 ITGB3 Chromosome 17 source: Human Genome Project

Chromosome anomalies Cause their effects by altering the amounts of products of the genes involved. Three copies of genes (trisomies) = 1.5 times normal amount. One copy of genes (deletions) = 0.5 times normal amount. Altered amounts may cause anomalies directly or may alter the balance of genes acting in a pathway.

Classification of chromosomal anomalies Numerical (usually due to de novo error in meiosis) Aneuploidy - monosomy - trisomy Polyploidy - triploidy Structural (may be due to de novo error in meiosis or inherited) Translocations - reciprocal - Robertsonian (centric fusion) Deletions Duplications Inversions Different cell lines (occurs post-zygotically) Mosaicism

Anomalies of chromosome structure Translocations Deletions Duplications Ring chromosomes Robertsonian Reciprocal

Chromosomal deletions and duplications (not caused by translocations) Are usually “one off”/de novo events occurring in meiosis. Have a very low recurrence risk in future pregnancies.

Most frequent numerical anomalies in liveborn Autosomes Down syndrome (trisomy 21: 47,XX,+21) Edwards syndrome (trisomy 18: 47,XX,+18) Patau syndrome (trisomy 13: 47,XX+13) Sex chromosomes Turner syndrome 45,X Klinefelter syndrome 47,XXY All chromosomes Triploidy (69 chromosomes)

The Karyotype A normal male chromosome pattern would be described as: 46,XY. 46 = total number of chromosomes XY = sex chromosome constitution (XY = male, XX = female). Any further description would refer to any abnormalities or variants found (see following slide for examples).

The Karyotype: an international description Total number of chromosomes, Sex chromosome constitution, Anormalies/variants. 46,XY 47,XX,+21 47,XXX 69,XXY 45,XX,der(13;14)(q10;q10) 46,XY,t(2;4)(p12;q12) 46,XX,del(5)(p25) 46,XX,dup(2)(p13p22) 46,XY,inv(11)(p15q14) 46,XY,fra(X)(q27.3) 46,XY/47,XXY Karyotypes are described by an internationally recognised format. The number refers to the number of chromosomes whilst the X and Y refer to the sex chromosomes, e.g. 46 XX would be a healthy female,46 XY a healthy male. Thereafter any chromosomal abnormalities or findings are described by recognised abbreviations and location is given of the affected part of the chromosome. e.g. 46,XX,dup(2)(p13p22) describes a female with 46 chromosomes and a duplication of the short arm of chromosome 2 from bands 13 -22.

The Karyotype: an international description Total number of chromosomes, Sex chromosome constitution, Anomalies/variants. 46,XY 47,XX,+21 Trisomy 21 (Down syndrome) 47,XXX Triple X syndrome 69,XXY Triploidy 45,XX,der(13;14)(p11;q11) Robertsonian translocation 46,XY,t(2;4)(p12;q12) Reciprocal translocation 46,XX,del(5)(p25) Deletion tip of chromosome 5 46,XX,dup(2)(p13p22) Duplication of part of short arm Chr 2 46,XY,inv(11)(p15q14) Pericentric inversion chromosome 11 46,XY,fra(X)(q27.3) Fragile X syndrome 46,XY/47,XXY Mosaicism normal/Klinefelter syndrome

Chromosomal findings in early miscarriages 40% apparently normal 60% abnormal: Trisomy (47 chromosomes – one extra) 30% 45,X (45 chromosomes – one missing) 10% Triploidy (69 chromosomes – three sets) 10% Tetraploidy (92 chromosomes – four sets) 5% Other chromosome anomalies 5% (e.g. structural anomalies)

Summary of Chromosome Anomalies Change in number e.g. trisomy 21 Down syndrome; Edwards’ syndrome; Turner syndrome. Usually an isolated occurrence. Change in structure e.g. translocations May be inherited. Down’s Syndrome An example of a chromosomal abnormality which causes learning difficulties The karyotype shows a case of Down’s syndrome (trisomy 21) For more information about Down’s syndrome, visit: www.screening.nhs.uk/downs/index.htm [NOTES FOR TRAINING FACILITATORS IN CASE OF QUESTIONS ONLY In total, there are normally 23 pairs of chromosomes, but in a trisomy there is an extra chromosome (tri somy = three bodies) A normal karyotype is written 46,XY or 46,XX The karyotype, or complement of chromosomes, seen in a regular trisomy 21 is written as 47,XX +21 if female or 47, XY +21 if male Note that Down’s syndrome can be inherited, although this is rare. These cases are due to a change in chromosome structure (a translocation)] Trisomy 21