GENERAL GENETICS

Ayesha M. KhanSpring 2013

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

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

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

Staining

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

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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

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Chromosome rearrangements

4 types– Duplications

– Deletions

– Inversions

– Translocations

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

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

Gene dosage

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

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

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

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

Paracentric inversion loop

Inversion loops

• Pericentric inversion loops– Crossing over within

loop creates recombinant chromosomes with duplications and deletions• nonviable

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