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Chapter 9 – Chromosomal Variation Chromosome Morphology • Metacentric – Centromere is centrally located; arms equal length • “p” and “q” – “p” is smaller when there is a size difference • Submetacentric – Centromere is off center • Acrocentric – Centromere is close to one end – p arm has satellites (knobs on stalks) • 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 • 1, 9, 16, Y • 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 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 – 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 • Large deletions can be seen cytogenetically; microdeletions by FISH • 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 Pericentric inversion loops 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 Robertsonian translocation • Between two acrocentric chromosomes – 13, 14, 15, 21, 22 • 2 q arms are joined at a common centromere – Forms a metacentric chromosome if two chromosomes are same size • Small fragment is usually lost – Tends to be acentric Translocations • Translocated chromosome is named after the chromosome that is the origin of the centromere • Heterozygotes have one normal copy of a chromosome, and one translocated one – During meiosis, all 4 chromosomes will associate – Can segregate 1 of 3 ways Translocation segregation • Alternate – Both normals go to one pole; both translocated go to the other • Balanced; viable • Adjacent 1 – Each pole gets one normal, and the opposite translocated – Partial monosomies/partial trisomies • inviable • Adjacent 2 – Each pole gets both the normal and translocated of the same chromosome – Inviable; rare Translocation segregation Fragile sites • Under certain conditions/culturing techniques, chromosomes develop breaks/restrictions at particular locations • Now routinely tested for by FISH analysis Aneuploidy • Abnormal number of chromosomes – Caused by: • Loss of chromosome during cell division; random error or loss of centromere; nondisjunction • Robertsonian translocation • Types – Nullisomy 2n – 2 – missing both members of a homologous pair – Monosomy 2n – 1 – missing one chromosome – Trisomy 2n + 1 – one extra chromosome – Tetrasomy – 2n + 2 – two extra chromosomes of the same type/homologous Aneuploidy • Alters phenotype dramatically – Often lethal if constitutional • Can see elaborate abnormalities in tumor cells – X inactivation in mammals takes care of extra Xs, so not as severe • Down syndrome – Primary • 3 free copies of #21 – Familial • Extra copy due to translocation – Can be involved in Robertsonian translocation – Parent can have 45 chromosomes, but have normal phenotype since all genetic material is present Uniparental Disomy • Both chromosomes of a homologous pair from the same parent • Probably originated from a trisomy – One chromosome is lost early in development • Recessive diseases – One carrier parent and one normal parent can have an affected child Mosaicism • Nondisjunction in later development can cause “patchiness” – normal cells and abnormal cells • Approximately 50% of Turner syndrome can be mosaics – 45, XO/46, XX Polyploidy • Extra sets of chromosomes – Triploid – 3n; tetraploid – 4n • Common in plants – more tolerant of extra sets of chromosomes • Autopolyploidy – Extra set is from same species • Error in cell division – Extra chromosome caused pairing problems; especially with odd numbers • 3n usually sterile; produce small seeds – Bananas; “seedless” watermelon Polyploidy • Allopolyploidy – Hybridization between two species – AABBCC x GGHHII – F1 generation ABCGHI – not homologous • Gametes are inviable, but may be able to reproduce asexually – Nondisjunction error can lead 2x, which could then reproduce sexually