Lecture 16: Errors in Meiosis Notes

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Hamish Spencer Profile

  • Sesquicentennial Distinguished Professor in Zoology & Genetics at Otago.

  • Research Interests: Population-genetic Theory, Genomic Imprinting, Phylogenetics, Phenotypic Plasticity, NZ Molluscs, History of Eugenics

  • Email: hamish.spencer@otago.ac.nz

Lecture 16: Errors in Meiosis - Objectives

  • Outline chromosomal aberrations (nondisjunction, aneuploidy, deletion, duplication, inversion, translocation) and their consequences in humans.

  • Describe how chromosomal rearrangements happen and behave at meiosis, and their contribution to birth defects in humans.

  • Outline the various forms of polyploidy and their consequences for meiosis and fertility.

  • Explain the effects of odd numbers of chromosomes in meiotic segregation.

Meiotic Disjunction

Review of Meiosis I & II:

  • Anaphase I: Correct disjunction of homologous chromosomes.

  • Anaphase II: Correct disjunction of sister chromatids.

Meiotic Nondisjunction

  • Definition: Failure of chromosomes to separate (disjoin) properly during meiosis.

  • Meiosis I: Homologous chromosomes do not separate.

  • Meiosis II: Sister chromatids do not separate.

  • Can also occur in mitosis.

  • Centromeric regions of nondisjoined chromosomes.

Aneuploidy

  • Meiotic nondisjunction results in gametes with an abnormal number of a particular chromosome.

  • Fusion of these gametes with a normal gamete results in a zygote with an abnormal number of a particular chromosome – aneuploidy.

  • Few aneuploid conditions are viable in humans.

Monosomy and Trisomy

  • Monosomic: Fertilization involving a gamete with no copy of a particular chromosome results in a missing chromosome in the zygote (2n-1).

  • Trisomic: A chromosome is present in triplicate in the zygote.

  • Monosomy and trisomy occur in 10-25% of all human conceptions.

  • Survival usually involves a set of traits caused by the abnormal gene dose associated with the extra or missing chromosomes.

Aneuploidy Example Karyotypes

  • Monosomic Individual: Chromosome 9

  • Trisomic Individual: Chromosome 21 (Down Syndrome)

Down Syndrome

  • Autosomal aneuploid condition.

  • Trisomy 21 (3 copies of chromosome 21).

  • Karyotypes have 47 chromosomes.

Down Syndrome Incidence

  • 1 in 750 live births.

  • Incidence increases with maternal age.

  • 40% of all cases arise where maternal age > 45.

Klinefelter Syndrome

  • Aneuploid condition of a sex chromosome (XXY).

  • Individuals have an extra copy of chromosome X.

  • Karyotypes have 47 chromosomes.

Turner Syndrome

  • Aneuploid condition of a sex chromosome (XO).

  • Individuals have only one chromosome X.

  • Karyotypes have 45 chromosomes.

Common Human Aneuploids

  • Down Syndrome: Trisomy 21, Male & Female, 1/750

  • Patau Syndrome: Trisomy 13, Male & Female, 1/5000

  • Edwards Syndrome: Trisomy 18, Male & Female, 1/10000

  • Klinefelter Syndrome: XXY, Male, 1/1000

  • Turner Syndrome: XO, Female, 1/5000

  • Supernumerary Y: XYY, Male, 1/1000

  • Supernumerary X: XXX, Female, 1/1000

  • Other: XXXX, Female, rare; XXXY, Male, rare; XXYY, Male, rare

Practice Question: Meiosis I Nondisjunction

If a pair of homologous chromosomes fails to disjoin at anaphase of meiosis I, the likely chromosome numbers (N) of the four resulting gametes will be:

  • (B) N+1, N+1, N-1, N-1.

Polyploidy

  • Possession of more than two complete chromosome sets.

  • May arise due to nondisjunction of all chromosomes in one gamete or failure of a diploid zygote to divide after replicating chromosomes during interphase.

  • Many polyploids are phenotypically normal.

  • One extra (or missing) chromosome appears to disrupt the genetic balance more than a complete set of chromosomes.

  • Example: A tetraploid (4n) zygote contains four complete sets of chromosomes.

Polyploidy and Infertility

  • Many polyploids are infertile due to possessing an odd number of chromosome sets.

  • Example: Bananas are triploid (3n). Unequal segregation during meiosis results in unbalanced gametes; therefore, they are infertile.

  • Polyploidy is common in the plant kingdom (e.g., strawberries are octoploids (8n)).

Polyploidy through Hybridization

  • Polyploidy can arise through hybridization.

  • Example: Hybridization between a radish and a brassica results in a polyploid raddage (4n) that is fertile.

  • The hybrid is initially sterile because chromosomes from different species don’t synapse.

  • Chromosome doubling allows synapse to occur, resulting in a fertile polyploid.

Polyploidy in Animals

  • Less common; found in some fish, insects, leeches, flatworms, and amphibians.

  • Animal polyploids often reproduce parthenogenetically.

  • Example: Triploid Parthenogenetic Lizard: New Mexico Whiptail.

Practice Question: Canola Chromosomes

Cabbage has 2n = 18 chromosomes, and turnip has 2n = 20. Canola is a polyploid derived from these two Brassica species and is fully fertile. Expected chromosome number for canola:

  • (B) 19

Other Chromosomal Aberrations

  • Loss, gain, or rearrangement of parts of chromosomes during synapsis.

  • Breakage in a chromosome can result in changes to chromosome structure: deletion, duplication, inversion, or translocation.

Deletions

  • When a chromosome breaks and a portion is lost, the missing piece is called a deletion.

  • Even small deletions can have severe effects and/or be lethal.

  • Deletions usually result in a loss of genes but do not change the order of the remaining genes.

Deletion Example: Cri du chat Syndrome

  • Results from the deletion of a small portion of chromosome 5.

  • Results in only one copy of the genes in this region.

Duplications

  • When part of a chromosome is present more than once in the genome, it results in a duplication.

  • May arise when a broken fragment of one chromosome reattaches as an extra segment to a sister or non-sister chromatid.

  • Duplications usually change the number of some genes on a chromosome but do not change the order of the remaining genes.

  • Duplications tend to have harmful effects.

Inversions

  • When part of a chromosome is inverted (turned around 180º) within a chromosome.

  • Requires breaks at two points along the length of the chromosome and subsequent insertion of the inverted segment.

  • Inversions do not change the number of genes on a chromosome but will change the linear order of genes within the inverted segment.

Consequences of Inversions

  • Inversions result in a change to the order of genes within the inverted segment.

  • Consequences on fertility may be more complex.

  • Inversions can cause problems in meiosis, as homologous chromosomes cannot align exactly.

  • Crossing over can then lead to deletions and duplications.

Translocations

  • A segment of a chromosome attaches to a nonhomologous chromosome.

  • Translocations usually do not change the overall number of genes, but they can sometimes change gene expression.

Translocations: Familial Down Syndrome

  • In familial Down syndrome, one parent is the carrier of a 14/21 translocation.

  • This type of translocation can arise when, following a breakage, the majority of chromosome 21 attaches to chromosome 14.

  • The parent that carries a 14/21 is phenotypically normal, even though they only have 45 chromosomes.

Familial Down Syndrome (cont.)

  • During synapsis, the 14/21 translocation chromosome may result in a gamete that has two copies of chromosome 21 (a normal chromosome 21 and one attached to chromosome 14).

  • When fertilized, the resulting zygote will have 46 chromosomes but three copies of chromosome 21.

  • Familial Down syndrome is heritable.

Translocations: Philadelphia Chromosome

  • Translocations may also arise during mitosis and some have been implicated in certain cancers.

  • During mitosis in some cells, a large portion of chromosome 22 is reciprocally translocated with a small portion of chromosome 9.

  • This translocation results in cancer due to the formation of a new ‘fused’ gene on chromosome 22 (Philadelphia chromosome).

  • 95% of patients with chronic myeloid leukemia carry the Philadelphia chromosome.

Summary of Chromosomal Aberrations

  • Diagram showing the frequency of different chromosomal aberrations in 1,000,000 human conceptions.

Practice Question: Familial Down Syndrome Karyotypes

Individuals with familial Down Syndrome have which of the following karyotypes?

  • (B) 46 chromosomes; translocation of 21

Lecture 16 Summary

  • Chromosomal aberrations, including nondisjunction, aneuploidy, deletion, duplication, inversion, and translocation, arise from errors during cell division.

  • These can contribute to birth defects in humans by disrupting how much protein is made (sometimes less or sometimes more than expected).

  • Translocations and inversions can disrupt pairing of homologous chromosomes during meiosis, resulting in unbalanced gametes and/or reduced fertility.

  • Polyploidy occurs when organisms have more than two complete sets of chromosomes.

  • In organisms with odd numbers of chromosomes (aneuploidy), or odd sets of chromosomes (e.g., triploid), chromosomes cannot evenly segregate, often resulting in sterility due to unbalanced gametes.

Objective-Based Questions (Revision)

  • Outline what happens if a non-disjunction event occurs during meiosis? If n=haploid number of chromosomes, list the chromosome number in the 4 products of meiosis if non-disjunction occurs during meiosis II.

  • Identify the type of chromosomal aberration in diagrams (a) – (d) below:

  • What do the terms aneuploidy and polyploidy mean?

  • Describe the challenges triploid organisms face in producing viable gametes and how this affects their reproductive abilities.

  • Why are some polyploid species fertile and able to successfully reproduce while others are sterile?

  • Chromosomal Aberrations and Their Consequences:

    • Nondisjunction: Failure of chromosomes to separate properly during meiosis, leading to aneuploidy.

    • Aneuploidy: Abnormal number of a particular chromosome, resulting in conditions like Down Syndrome (Trisomy 21).

    • Deletion: Loss of a portion of a chromosome, potentially causing severe effects like Cri du chat syndrome.

    • Duplication: Part of a chromosome is present more than once, often leading to harmful effects.

    • Inversion: Part of a chromosome is inverted, which can cause problems during meiosis due to misalignment of homologous chromosomes, leading to deletions and duplications after crossing over.

    • Translocation: A segment of a chromosome attaches to a nonhomologous chromosome, potentially affecting gene expression and causing conditions like Familial Down Syndrome or Philadelphia chromosome in chronic myeloid leukemia.

  • Chromosomal Rearrangements, Meiosis, and Birth Defects:

    • Chromosomal rearrangements such as deletions, duplications, inversions, and translocations occur due to breakage in chromosomes during synapsis.

    • Inversions and translocations can disrupt the pairing of homologous chromosomes during meiosis, resulting in unbalanced gametes and reduced fertility. These rearrangements can lead to birth defects by disrupting the amount of protein produced.

  • Polyploidy: Forms, Consequences for Meiosis, and Fertility:

    • Polyploidy is the condition of having more than two complete sets of chromosomes.

    • It can arise through nondisjunction of all chromosomes in a gamete or hybridization between different species.

    • Polyploidy often leads to infertility, especially when there is an odd number of chromosome sets, causing unequal segregation during meiosis and unbalanced gametes. However, some polyploid species can be fertile if chromosome doubling allows for proper synapse.

  • Effects of Odd Numbers of Chromosomes in Meiotic Segregation:

    • Aneuploidy (odd numbers of individual chromosomes) or triploidy (odd number of chromosome sets) results in uneven segregation during meiosis.

    • This leads to the production of unbalanced gametes, often resulting in sterility due to the inability to evenly segregate chromosomes.