Understanding Chromosome Morphology and Mutations: A Comprehensive Overview

1. GENERAL GENETICS Ayesha M. Khan Spring 2013

2. Chromosome Morphology • Metacentric • Centromere is centrally located; arms equal length • Submetacentric • Centromere is off center • Acrocentric • Centromere is close to one end • a long arm and a knob, or satellite, at the other • Telocentric • Centromere is at one end • Not present in humans

3. Karyotype • Complete set of chromosomes arranged in homologous pairs • Sample is from an actively dividing cell • Chemical inhibits spindle assembly formation • Cell can not complete mitosis • Hypotonic solution swells cell • Allows chromosomes to spread out • Dropped on slide and stained

4. Staining • G banding • Giemsa stain; most common • Stains A-T rich regions • C banding • Stains centromeric heterochromatin and portions of chromosomes with large sections of heterochromatin • R banding • Stains G-C rich regions • Gives opposite banding pattern of G banding • Q banding • UV light is used • Same pattern as G banding

5. Staining (a) G bands (b) Q bands (c) C-bands (d) R-bands

6. Types of chromosome mutations • Chromosomal rearrangement • Structure is altered • Aneuploidy • Abnormal number of chromosomes • Missing one or more/having one or more extra • Polyploidy • 1 or more additional sets of chromosomes

7. Chromosome rearrangements 4 types • Duplications • Deletions • Inversions • Translocations

8. Duplications • Section of chromosome is doubled • Tandem • Repeated segment is right after the original • Displaced • Repeated segment is located elsewhere on chromosome, or on a different chromosome • Reverse • Sequence is inverted from the original sequence

9. Duplications • Heterozygotes • During paring of homologous chromosomes, duplicated region loops out • Offspring receive two copies of involved genes from parent with duplication, and a third copy of the other parent • Partial trisomy for all involved genes • Alters gene dosage

10. Gene dosage

11. Deletions • Loss of a portion of chromosome • If the deleted region includes the centromere, entire chromosome will be lost • Usually lethal in homozygous form • Heterozygotes • Normal chromosome must loop out during pairing • Partial monosomy for all involved genes

12. Deletions - heterozygotes • Affects gene dosage • Pseudodominance • Expression of mutant/recessive phenotype due to loss of normal/dominant copy • Haploinsufficiency • Both copies of the gene are needed to manufacture adequate amount of gene product • One gene doesn’t produce enough for a normal phenotype

13. Inversions • Two breaks in chromosome, then flipped and reinserted • Paracentric inversion • Both breaks occur in one arm • Pericentric inversion • Breaks on both arms; centromere is involved • Can change morphology by altering centromere position • Effects • Disruption of a gene – no functional product • Position effect • Change in gene position can affect gene expression

14. Inversion loops • Chromosomes have to loop when pairing • Paracentric inversion loops • If crossing over occurs within loop: • Creates a dicentric chromosome and an acentric chromosome • Acentric is lost • Dicentric forms a dicentric bridge, and breaks • Nonviable recombinant gametes

15. Paracentric inversion loop

16. Inversion loops • Pericentric inversion loops • Crossing over within loop creates recombinant chromosomes with duplications and deletions • nonviable

17. Translocations • Rearranges genetic material to another part of the same chromosome; or nonhomologous chromosome • Nonreciprocal • Segment moves from one chromosome to another • Reciprocal • Exchange between two chromosomes • Effects • Loss of gene function – break • Position effect • Creation of a fusion/abnormal protein