Presentation on theme: "Chromosomes An overview"— Presentation transcript:
1Chromosomes 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.
2Chromosomes This presentation includes: The anatomical structure of chromosomesClassification of chromosomal anomaliesDescription of chromosomal anomaliesExamples of chromosomal anomaliesExplanation of normal and abnormal karyotypesChromosomal findings in early miscarriages.
3Chromosomes 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 parentChromosome 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 fatherAsk participants - what sex is this individual? (Male, XY)Gene for sickle cell disease (chromosome 11)
5Chromosomes as seen at metaphase during cell division Telomere DNA and protein cap Ensures replication to tip Tether to nuclear membraneLight bands Replicate early in S phase Less condensed chromatin Transcriptionally active Gene and GC richShort arm p (petit)Centromere Joins sister chromatidsEssential for chromosome segregation at cell division 100s of kilobases of repetitive DNA: some non-specific, some chromosome specificLong arm qDark (G) bands Replicate late Contain condensed chromatin AT richTelomere
6Human chromosome banding patterns seen on light microscopy Different chromosome banding resolutions can resolve bands, sub-bands and sub-sub-bands
7A 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)
8Total Genes On Chromosome: 723 373 genes in region marked red, 20 are shownFZD2AKAP10ITGB4KRTHA8Genes are arranged in linear order on chromosomesWD1SOSTMPP3MLLT6STAT3BRCA1breast cancer 1, early onsetGFAPNRXN4NSFNGFRCACNB1HOXB9HTLVRABCA5CDC6ITGB3Chromosome 17 source: Human Genome Project
9Chromosome anomaliesCause 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.
10Classification of chromosomal anomalies Numerical (usually due to de novo error in meiosis) Aneuploidy - monosomy trisomy Polyploidy - triploidyStructural (may be due to de novo error in meiosis or inherited) Translocations - reciprocal Robertsonian (centric fusion) Deletions Duplications InversionsDifferent cell lines (occurs post-zygotically) Mosaicism
11Anomalies of chromosome structure TranslocationsDeletionsDuplicationsRing chromosomesRobertsonianReciprocal
12Chromosomal 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.
14The KaryotypeA normal male chromosome pattern would be described as:46,XY.46 = total number of chromosomesXY = sex chromosome constitution(XY = male, XX = female).Any further description would refer to any abnormalities orvariants found (see following slide for examples).
15The Karyotype: an international description Total number of chromosomes,Sex chromosome constitution,Anormalies/variants.46,XY47,XX,+2147,XXX69,XXY45,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,XXYKaryotypes 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
16The Karyotype: an international description Total number of chromosomes,Sex chromosome constitution,Anomalies/variants.46,XY47,XX, Trisomy 21 (Down syndrome)47,XXX Triple X syndrome69,XXY Triploidy45,XX,der(13;14)(p11;q11) Robertsonian translocation46,XY,t(2;4)(p12;q12) Reciprocal translocation46,XX,del(5)(p25) Deletion tip of chromosome 546,XX,dup(2)(p13p22) Duplication of part of short arm Chr 246,XY,inv(11)(p15q14) Pericentric inversion chromosome 1146,XY,fra(X)(q27.3) Fragile X syndrome46,XY/47,XXY Mosaicism normal/Klinefelter syndrome
17Chromosomal findings in early miscarriages 40% apparently normal60% 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)
18Summary of Chromosome Anomalies Change in numbere.g. trisomy 21 Down syndrome; Edwards’ syndrome; Turner syndrome.Usually an isolated occurrence.Change in structuree.g. translocationsMay be inherited.Down’s SyndromeAn example of a chromosomal abnormality which causes learning difficultiesThe karyotype shows a case of Down’s syndrome (trisomy 21)For more information about Down’s syndrome, visit:[NOTES FOR TRAINING FACILITATORS IN CASE OF QUESTIONS ONLYIn 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,XXThe karyotype, or complement of chromosomes, seen in a regular trisomy 21 is written as 47,XX +21 if female or 47, XY +21 if maleNote 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