Explanation slides - Chromosomes
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Transcript of Explanation slides - Chromosomes
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
ChromosomesAn 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.
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
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.
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
Chromosomes
• 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.
Gene for sickle cell disease (chromosome 11)
Gene for cystic fibrosis (chromosome 7)
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
Chromosomes
ppCentromereCentromere
Chromosome 5Chromosome 5
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
CentromereJoins sister chromatids
Essential for chromosome segregation at cell division100s of kilobases of repetitive DNA: some non-specific, some chromosome specific
Dark (G) bands Replicate lateContain condensed chromatinAT rich
Short armp (petit)
Long armq
Light bands Replicate early in S phaseLess condensed chromatinTranscriptionally activeGene and GC rich
TelomereDNA and protein capEnsures replication to tipTether to nuclear membrane
Telomere
Chromosomes as seen at metaphase during cell division
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
Different chromosome banding resolutions can resolve bands, sub-bands and sub-sub-bands
Chromosome 1
Human chromosome banding patterns seen on light microscopy
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
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)
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
Total Genes On Chromosome: 723373 genes in region marked red, 20 are shown
FZD2AKAP10ITGB4KRTHA8WD1SOSTMPP3MLLT6STAT3BRCA1breast cancer 1, early onsetGFAPNRXN4NSFNGFRCACNB1HOXB9HTLVRABCA5CDC6ITGB3
Chromosome 17source: Human Genome Project
Genes are arranged in linear order on chromosomes
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
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.
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
Classification of chromosomal anomalies
• Numerical (usually due to de novo error in meiosis)Aneuploidy - monosomy- trisomyPolyploidy - triploidy
• Structural (may be due to de novo error in meiosis or inherited) Translocations - reciprocal
- Robertsonian (centric fusion)DeletionsDuplicationsInversions
• Different cell lines (occurs post-zygotically) Mosaicism
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
Anomalies of chromosome structure
• Translocations
• Deletions• Duplications• Ring chromosomes
RobertsonianReciprocal
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
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.
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
Most frequent numerical anomalies in liveborn
AutosomesDown syndrome (trisomy 21: 47,XX,+21)
Edwards syndrome (trisomy 18: 47,XX,+18) Patau syndrome (trisomy 13: 47,XX+13)
Sex chromosomesTurner syndrome 45,X
Klinefelter syndrome 47,XXY
All chromosomesTriploidy (69 chromosomes)
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
The Karyotype
A 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).
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
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,XXY
The Karyotype: an international description
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
Total number of chromosomes,
Sex chromosome constitution,
Anomalies/variants.46,XY47,XX,+21 Trisomy 21 (Down syndrome)47,XXX Triple X syndrome69,XXY Triploidy
45,XX,der(13;14)(p11;q11) Robertsonian translocation46,XY,t(2;4)(p12;q12) Reciprocal translocation
46,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
The Karyotype: an international description
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
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)
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk
Summary 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.
Trisomy 21