Chromosomes

这是一篇关于Chromosomes的思维导图，主要内容有Structure、 Abnormalities、Technologies 、Definations。

Chromosomes

• Structure
  • Banding patterns
    • Please pay attention, the directions of region, band and subband are the opposites on the p and q arms
  • Way to write chromosome locations
    • 1. chromosome number
    • 2. Arm
    • 3.region
    • 4. band
    • 5. subband
      • If there is a subband, it requires a dot between the band and the subband
  • Differenciate chromosomes
    • metacentric
      • p=q
    • submetacentric
      • p＜q
    • acrocentric
      • p→0
        • p is so short to hard to observe, but still present
        • in human: 13,14,15,21,22, (Y)
    • telocentric
      • p=0
    • subtelocentric
      • p<p+q/4
        • p<q/3
    • holocentric
      • p,q∈∅
• Abnormalities
  • Numbers change
    • Aneuploidy
      • occur in 15% human live birth, but 99% of them are lethan therefore not born
      • • • The reason is listed here( the number is the disease causing gene identified by OMIM)
      • Viable Aneuploidy
      • The reason: Nondisjunction
        • could be either meiosis stage 1/2
  • Structural change
    • Partial Aneuploidy
      • Duplication, deletion, or translocation of a chromosomal segment results in haploid or triploid dosage of only the region of the affected genes
    • Rearangement
      • translocation
        • Breaks accoured in 2 different chromosomes
        • It's possible between all chromosomes
        • 3 main categories
          • Reciprocal or balanced
            • no overall gain or loss of genetic information
            • Usually no phenotype, but some times it causes cancer through the position effect
          • Robertsonian
            • Reciprocal exchange between acrocentric chromosomes generate large metacentric chromosome and small chromosome, which may lost during cell division.
          • Non-reciprocal/unbalanced
            • Unbalanced exchange involves loss of chromosomal materials
              • Cause lethal partial monosomy
      • Deletion
        • Homozygosity
          • Del/Del
            • lethal
        • Hemizygosity
          • Del/Y
            • mostly lethal
            • Exception: 80 kb Del containing white (w) gene in lab fly.
        • Heterozygosity
          • Del/+
            • viable but usually detrimental
            • Effects
              • Deletion loop
              • might uncover the recessive gene to show phenotype: psuedodominance
      • Duplication
        • Cause
          • Mostly caused by misaligned homologous recombination, or chromosomal breakages
        • defination
          • Doubling of chromosome segments
            • The duplicates can be adjecent with the original segments (tandem), or dispersed, each of them can be in same or reversed orders.
        • effects
          • Duplication loops in prophase I
          • Unequal crossing over
          • No phenotypic effects
          • Trisomy
          • Evelutionary responses for multigene family
      • Inversion
        • Cause
          • 1. (most) 180 rotation of chromosomal region after two double strands breaks.
          • 2. (Rare) Intrachromosomal crossover
        • Consequence
          • Invertion heterozygoes reduces the number of recombinant progeny
            • It forms super gene
          • inv(9)(p12q13) in human is normal
      • Isochromosome
        • defination
          • A chromosome Losses one of its arm and replaces the exact copy of the left arm.
        • i(X)(q10) is most common
        • 10% of isochromosmes can leads to tumor development
          • RB
          • AML
      • Ring chromosome
        • The breaks are in two arms and they form a ring structure
    • Chromosomal Fragile Sites (cfra)
      • cfra are weaknesses at specific sites appearing as gaps or constrictions, often at the junctions between bands
  • Caused by two or more, simultaneous breaks in the chromosome set
• Technologies
  • FISH
  • Somatic cell hybridization
    • Above is how we knock out chromosomes
    • Then we can correlate the gene products and the presence of the chromosome
      • or we can use probes to specify the specific regions
  • Loci Mapping
    • 3 markers
      • RFLPs: Restriction fragment length polymorphisms
      • SSRs/STRs: simple sequence repeats/small tandem repeats (microsatellites)
      • SNPs: single nucleotide polymorphisms
        • Haplotype and Tag SNPs
        • 500,000 or more tag SNPs are identified
          • 85% of the human genome falls into haplotype blocks
        • It must has 2 or 3 variations in that site!(not four)
          • The variations should be polymorphisms, which means the allel frequencies should all beyond 0.01
• Definations
  • Karyotype
    • visual presentation of the complete set of chromosomes in a cell
  • Haplotype
    • a combination of alleles (DNA sequences) at adjacent locations (loci) on the chromosome that are transmitted together.
    • it may be one locus, several loci, or an entire chromosome depending on the number of recombination events that have occurred between a given set of loci
  • Euploid (Euploidy)
    • carrying only complete sets of chromosomes (nN) (n: integrals).
  • Polyploid (Polyploidy)
    • carrying three or more complete sets of chromosomes (>3N).
  • Genetic Mosaic
    • an individual with cells of mixed genotype: diploid and polyploid
  • Aneuploid
    • carrying chromosome numbers not an exact multiple of the haploid number (N)
    • monosomic (monosomy): 2n-1, trisomic (trisomy): 2n+1 tetrasomic (tetrasomy): 2n+2
  • Rearragement
    • The chromosomal mutation caused by 2 or more double strand breaks and the mistaked rejoin