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 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 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 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

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 Types 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 Down syndrome 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