GENERAL GENETICS Ayesha M. Khan Spring 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 On human chromosomes, the short arm is designated by the letter p and the long arm by the letter q.

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 A picture of metaphase chromosomes lined up in descending order of their size

Staining G banding C banding R banding Q 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

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

Chromosome rearrangements 4 types Duplications Deletions Inversions Translocations

Duplications Section of chromosome is doubled Tandem Displaced Reverse 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 abnormal gene dosage: imbalances in the amounts of gene products

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