Mutations

• Submetacentric: A centromere is located in the middle of the chromosome.
• Metacentric: chromosomes with the centromere right in the middle
• Acrocentric: The centromere is at the near top of the chromosome.
• Telocentric: centromeres in the telomeric region. Tip of chromosome.
• A chance of a chromosomal abnormality: 1/154 babies.
• Types of chromosomal abnormalities:

  • Aneuploidy
  • Polyploidy
  • Structural abnormalities
• Aneuploidy from a non- disjunction:

  • At meiosis II, the 2 daughter cells divide into 4, however one ends up with 2 sister chromatids and the other with none.
  • The sperm fertilises the the daughter cells forming abnormal zygotes one called a triploid with 3 chromosomes and the other a monoploid with 1 set of chromsomes.
• Triploids are usually not viable as they have an extra copy of every gene which can lead to development problems or death during embryonic stage.
• Monoploids are also not viable because there is only one copy of genes so if it's missing any important ones then that will cause issues.
• Nondisjunction can occur in meiosis 1 or 2, in meiosis 1, the diploid cell divides forming two cells one with two sets of chromosomes, the other with none. The cells further divide into four haploid cells. Each with a pair of chromosomes and the other 2 with none. sperm binds forming monoploids and triploids
• sperm cells may also carry more than one chromatid, forming non viable triploids or duploids.
• A karyotype is the observed characteristics (number, type, shape, etc.) of the chromosomes of an individual or species.
• karyotyping:

  5ml venous blood -> Add phytohemagglutinin -> culture at 37*C for 3 days -> Add colchicine and hypotonic saline -> cells fixed -> spread cells onto slide via dropping -> digest with trypsin and stain with Giesma -> analyse metaphase spread -> karyotype
• In order to observe chromosomes during karyotyping, cells are treated with chemicals (such as colchicine) that arrest them in metaphase, a stage of cell division where chromosomes are highly condensed and visible.
• Q-banding: Fluorescent stain quinacrine stains AT - rich regions
• Q-banding:

  • This technique uses a fluorescent stain called quinacrine, which specifically binds to regions of DNA that are rich in adenine and thymine (AT-rich regions).
  • When viewed under a microscope, the stained chromosomes show distinct fluorescent patterns, allowing scientists to identify and study specific regions of the chromosomes.
• G-banding:

  • G-banding is one of the most widely used techniques in karyotyping.
  • It involves staining the chromosomes with a dye called Giemsa, which also binds preferentially to AT-rich regions of DNA.
  • The stained chromosomes exhibit characteristic dark and light bands, which are formed due to differences in the density of DNA along the chromosome.
  • These banding patterns are almost identical to those produced by Q-banding.
• 1. R-banding:

  • In R-banding, chromosomes are stained using a method that involves the reverse application of the Giemsa stain.
  • This technique specifically highlights regions of DNA that are rich in guanine and cytosine (GC-rich regions).
  • The resulting banding pattern is the inverse of G-banding, with GC-rich regions appearing dark and AT-rich regions appearing light.
• 1. C-banding:

  • C-banding involves staining chromosomes with Giemsa after denaturing the DNA, which reveals regions of DNA near the centromere.
  • The centromere is the region of the chromosome that plays a crucial role in cell division.
  • By staining after denaturation, C-banding allows scientists to visualize and study the structure of the centromeric regions.
• Q banding:

  
• G banding:

  
• Ideograms:

  ❑ stylised version of karyogram

  ❑ easier to interpret
• ❑ Haploid (n):

  ✓ having a single set of chromosomes without homologous pairs eg gametes

  ❑ Diploid (2n):

  ✓ having two homologous copies of each chromosome eg normal human cells

  ❑ Euploidy (Xn):

  ✓ having a multiple of the normal haploid number of chromosomes eg 23, 46, 69, 92

  ❑ Aneuploidy (2n +/- X):

  ✓ not being in euploidy eg extra copy of a single chromosome
• ❑ Triploidy:

  ✓ one complete extra set of chromosomes.

  ✓ Usually caused by polyspermy, the fertilisation of an egg by more than one sperm.

  ✓ embryos usually spontaneously abort.
• Tetraploidy:

  ✓ Usually the result of a failure of the first zygotic division. It is also lethal to the embryo.

  ✓ Any other cell division may also fail to complete properly and in consequence a very small proportion of tetraploid cells can be found in normal individuals
• Aneuploidy:

  ❑ Nullisomy (2n-2)

  ✓ Complete loss of a chromosomal pair. Lethal in very early embryogenesis.

  ❑ Monosomy (2n-1)

  ✓ All autosomal monosomies are lethal in very early embryogenesis.

  ❑ Trisomy (2n+1)

  ✓ Addition of extra copy of one chromosome. Most are lethal, several are viable.

  ❑ Aneuploidy causes gene dosage effects
• gene dosage effect: the number of copies of a gene which affects the characteristics of the organism.
• Group A (Chromosomes 1-3)


  • Large chromosomes that are metacentric, meaning the centromere is located near the middle, resulting in arms of approximately equal length
• Group B (Chromosomes 4-5)


  • Large chromosomes that are submetacentric, meaning the centromere is located off-center, resulting in one arm longer than the other
• Group C (Chromosomes 6-12)


  • Medium-sized chromosomes that are submetacentric
  • The X chromosome closely resembles pair number 6 and is the longest in this group
• Group D (Chromosomes 13-15)


  • Medium-sized chromosomes that are acrocentric, meaning the centromere is located near one end
  • All three pairs have satellites (small, knob-like structures) on the short arm
• Group E (Chromosomes 16-18)


  • The smallest of the medium-sized chromosomes
  • Pair 16 is metacentric (centromere in the middle), while the others are submetacentric
• Group F (Chromosomes 19-20)


  • Short chromosomes that are metacentric
• Group G (Chromosomes 21-22)


  • Very short chromosomes that are acrocentric
  • Both pairs have satellites on them
• Individuals with Klinefelter syndrome have one Y chromosome and two X chromosomes (XXY). The presence of the extra X chromosome can lead to various physical and developmental differences compared to typical males.
• Trisomy's:

  ❑ Trisomy 8 – Warkany syndrome 2

  ✓ Lethal in embryogenesis. Commonly mosaic. Physical abnormalities, developmental delay, mental retardation

  ❑ Trisomy 9 – Mosaicism

  ✓ Commonly mosaic. Various dysmorphisms including craniofacial. Developmental delay. Good survival rate.

  ❑ Trisomy 13 – Patau syndrome

  ✓ Wide variety of abnormalities, including polydactyly. Most die in first year of life.
• Trisomy 18 – Edwards syndrome

  ✓ most miscarry or are stillborn. Most die within first month due to severe abnormalities.

  ❑ Trisomy 22

  ✓ common in early spontaneous abortions

  ❑ Trisomy 21 – Down syndrome

  ✓ most survivable – often close to normal lifespan
• 5p- (Cri-du-chat Syndrome):

  • This condition is caused by a deletion of a portion of chromosome 5, specifically the short (p) arm. Hence, it is often referred to as "5p-" or "5p deletion syndrome."
  • ✓ distinctive, high-pitched, catlike cry in infancy
  • ✓ growth failure
  • ✓ microcephaly
  • ✓ facial abnormalities
  • ✓ profound intellectual disability throughout life
• Microcephaly refers to a smaller-than-normal head size. It is a common feature of Cri-du-chat syndrome.
• • Prader-Willi Syndrome: When the deletion occurs on the paternal chromosome 15, it results in Prader-Willi syndrome. This syndrome is characterized by feeding difficulties in infancy, followed by excessive eating and obesity later in childhood. Other features may include developmental delays, intellectual disability, short stature, and behavioral problems.