Meiosis Errors Lecture 16

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• Hamish Spencer is a Sesquicentennial Distinguished Professor in Zoology & Genetics.
• Research interests include population-genetic theory, genomic imprinting, phylogenetics, phenotypic plasticity, NZ Molluscs, and the history of eugenics.
• Lecture 16 focuses on errors in meiosis.

Lecture 16 Objectives

• You should be able to outline chromosomal aberrations and their consequences in humans
• You should be able to describe how chromosomal rearrangements happen and the effects on birth defects in humans
• You should be able to outline the forms of polyploidy and its consequences for meiosis and fertility
• You should be able to explain the effects of odd numbers of chromosomes in meiotic segregation

Meiotic Disjunction

• Meiosis I & II ensures correct disjunction of homologous chromosomes and sister chromatids.

Meiotic Nondisjunction

• Meiotic nondisjunction means chromosomes fail to separate properly during meiosis
• In Meiosis I, homologous chromosomes do not separate.
• In Meiosis II, sister chromatids do not separate.
• Nondisjunction can also occur in mitosis.

Aneuploidy

• Meiotic nondisjunction leads to gametes with an abnormal chromosome number.
• When these gametes fuse with a normal one, the zygote has an abnormal number of a particular chromosome, called aneuploidy.
• Very few aneuploid conditions are viable in humans.
• Fertilization involving a gamete lacking a chromosome copy results in a monosomic zygote (2n-1).
• A chromosome present in triplicate makes the zygote trisomic.
• Monosomy and trisomy are estimated to occur in 10-25% of human conceptions.
• Surviving organisms with aneuploidy usually exhibit traits caused by abnormal gene dosage associated with the extra or missing chromosomes.

Down Syndrome

• Down Syndrome is an autosomal aneuploid condition involving trisomy 21 (3 copies of chromosome 21)
• Karyotypes of individuals with Down Syndrome have 47 chromosomes.
• Down Syndrome occurs in 1 in 750 live births.
• The incidence of Down syndrome increases with maternal age.
• 40% of Down Syndrome cases arise when the maternal age is over 45.

Klinefelter Syndrome

• Klinefelter Syndrome (XXY) is an aneuploid condition of a sex chromosome.
• Individuals have an extra copy of the X chromosome, and their karyotypes have 47 chromosomes.

Turner Syndrome

• Turner Syndrome (XO) where there is an aneuploid condition of a sex chromosome (only one chromosome X).
• Karyotypes have 45 chromosomes.

Common Human Aneuploids

• Down Syndrome: 21 21 21 chromosomes, M & F sex, 1/750 incidence
• Patau: 13 13 13 chromosomes, M & F sex, 1/5000 incidence
• Edwards: 18 18 18 chromosomes, M & F sex, 1/10000 incidence
• Klinefelter: XXY chromosomes, M sex, 1/1000 incidence
• Turner: XO chromosomes, F sex, 1/5000 incidence
• Supernumerary Y: XYY chromosomes, M sex, 1/1000 incidence
• Supernumerary X: XXX chromosomes, F sex, 1/1000 incidence
• Other: XXXX chromosomes, F sex, rare incidence
• Other: XXXY chromosomes, M sex, rare incidence
• Other: XXYY chromosomes, M sex, rare incidence

Polyploidy

• Polyploidy is possessing more than two complete chromosome sets.
• It may arise from nondisjunction of all chromosomes in a gamete, or failure of a diploid zygote to divide after chromosome replication in the G2 phase.
• Many polyploids are phenotypically normal
• An extra or missing chromosome disrupts genetic balance more than a complete set of chromosomes.
• Polyploidy is common in the plant kingdom; strawberries are octoploids (8n).
• Many polyploids are infertile because of an odd number of chromosome sets.
• Bananas are triploid (3n); they are infertile due to unbalanced gametes during meiosis because homologous chromosomes do not segregate equally.
• Polyploidy can arise through hybridization.
• Polyploidy in animal species is less common; it's found only in a few fish, insects, leeches, flatworms and amphibian species.
• Animal polyploids often reproduce parthenogenetically.

Chromosomal Aberrations

• Loss, gain, or rearrangement of chromosome parts can occur during synapsis.
• Chromosome breakage can cause deletion, duplication, inversion, or translocation.

Deletions

• A deletion occurs when a chromosome breaks and a portion is lost.
• 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: Lejeune Syndrome

• Cri du chat (Lejeune syndrome) results from a deletion of a small portion of chromosome 5, causing only one copy of the genes in that region.

Duplications

• A duplication occurs when part of a chromosome is present more than once in the genome.
• It may arise if a broken chromosome fragment reattaches as an extra segment to a sister or non-sister chromatid.
• Duplications 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

• An inversion occurs when part of a chromosome is inverted (turned around 180°) within the chromosome.
• An inversion requires breaks at two points along the chromosome's length, followed by insertion of the inverted segment.
• Inversions do not change the number of genes on a chromosome but alter their linear order.
• Inversions can cause issues during meiosis because homologous chromosomes cannot align exactly, which can affect fertility.
• Crossing over can then lead to deletions and duplications.

Translocations

• Translocation occurs when a segment of one chromosome attaches to a nonhomologous chromosome.
• Translocations do not usually change the overall number of genes, but they can sometimes change gene expression.

Translocations: Familial Down Syndrome

• In familial Down syndrome, one parent carries a 14/21 translocation.
• The majority of chromosome 21 attaches to chromosome 14 following breakage.
• The parent carrying a 14/21 translocation is phenotypically normal, despite having 45 chromosomes.
• During synapsis, the 14/21 translocation chromosome may result in a gamete with two copies of chromosome 21.
• Fertilization of such a gamete results in 46 chromosomes, but three copies of chromosome 21.
• Familial Down syndrome is heritable.

Translocations: Philadelphia Chromosome

• Translocations can arise during mitosis and be implicated in certain cancers.
• A large portion of chromosome 22 is reciprocally translocated with a small portion of chromosome 9.
• This translocation results in cancer because of a new 'fused' gene on chromosome 22 (Philadelphia chromosome).
• 95% of patients with chronic myeloid leukemia carry the Philadelphia chromosome.

Lecture 16 Summary

• Chromosomal aberrations (nondisjunction, aneuploidy, deletion, duplication, inversion, translocation) arise from errors during cell division.
• These aberrations can cause birth defects by disrupting protein production levels.
• Translocations and inversions disrupt homologous chromosome pairing during meiosis, resulting in unbalanced gametes and/or reduced fertility.
• Polyploidy occurs when organisms have more than two complete chromosome sets.
• In organisms with odd chromosome numbers (e.g., triploid) or aneuploidy, chromosomes cannot evenly segregate, often causing sterility due to unbalanced gametes.