Test 1 - Chromosome Abnormalities

Trisomy 21 is caused by a failure of the 21st chromosome to separate during egg or sperm development.As a result, a sperm or egg cell is produced with an extra copy of chromosome 21; this cell thus has 24 chromosomes. When combined with a normal cell from the other parent, the baby has 47 chromosomes, with three copies of chromosome 21

Cite and explain one possible reason for the trisomy 21 disorder.

Deletion is more severe because this causes loss of genetic material, while inversion merely inverts the material 180 degrees

Compare phenotypic consequences of deletions and inversions. Which are more severe? Why?

Balanced gametes have undergone an even exchange of material with no extra or missing genetic information Unbalanced gametes have undergone an uneven exchange of material resulting in either extra or missing genetic information

Explain the difference between balanced and unbalanced gametes.

Fragile X Syndrome This is caused by expansion of trinucleotide repeats in the FMR1 (Fragile X mental retardation) gene on the X chromosome; resulting in a failure to express the fragile X mental retardation protein (FMRP), which is required for normal neural development.

Give an example of a human genetic disorder associated with fragile sites. Explain its mechanism.

b and d

Huntington's disease in humans is caused by (circle the correct answer(s)): a) A deletion in the HTT gene, located on the short arm of chromosome 4; b) More than 35 copies of the CAG-triplet in the HTT gene; c) A trisomy of chromosome 21; d) Massive expansion of trinucleotide repeats in the Huntingtin gene; e) The formation of the Philadelphia chromosome; f) None of the above.

It can lead to unequal crossing over between region-specific repeats

In a pair of homologous chromosomes, one homolog has a deletion. What will happen in pachytene?

Inversions/duplications/deletions affect a pair of homolgous chromosomes while translocations take place between non-homologous chromosomes

In which way do translocations differ from deletions, duplications and inversions? (Think in terms of homologous and non-homologous chromosomes).

*Redundancy of genetic material - overdose *Problems in meiotic pairing *Changes in phenotype - various disorders/diseases

Name the main consequences of duplications.

Deletions Duplications Inversions Translocations

Name the main structural aberrations that can occur in mammalian chromosomes?

Nonreciprocal Translocation Reciprocal Translocation

Name the two main types of translocations.

Paracentric Inversion Pericentric Inversion

Name the two types of inversions?

No. Trisomy 1 and 19 will never result in a pregnancy, spontaneous abortion, or liveborn due to their unique gene densities

Spontaneous abortions with trisomy of chromosome 1 or chromosome 19 are never seen. Do they ever occur? Why?

Monosomic zygotes die before implantation and there is no recognized pregnancy except for a few cases

Trisomy for many different chromosomes is routinely observed in spontaneous abortions, but monosomy is not. Why?

False It is rare in mammals and birds but common in reptiles

True or false? Cases of polyploidy are rare in mammals, birds and reptiles.

Paralogous genes are genes in the same species that resulted from gene duplications that share some sequence similarity but have distinct gene products and functions Ex. Gamma globins and Milk caseins

What are paralogous genes? Give an example.

Usually viable but can lead to subfertility or infertility and also mild mental and physical problems

What are the consequences of numerical aberrations in sex chromosomes for the organism?

Tetraploidy Mitotic failure in embryogenesis Cell fusion Triploidy Egg fertilized with two sperms Ovum fused with polar body and fertilized with haploid sperm Meiosis I or II errors in oo-or spermatogenesis

What are the germline events that can lead to human polyploidy?

13, 18, 21 Trisomy 21

What are the only three human chromosomes that can be trisomic in liveborns? Which is the most common among the three?

It can result in genetically unbalanced gametes. If these gametes participate in fertilization, lethality and semisterility may result.

What are the possible consequences of translocations for reproduction? Explain

Meiotic errors would lead to either a decreased or increased number of chromosomes within the organism

What are the usual consequences of meiotic errors in the number of chromosomes for the organism?

A deletion is a loss of any genetic material whether it be a single locus or larger segment This can lead to... *Loss of chromosome segment *Loss of gene(s) and gene products *Problems in meiotic pairing *Changes in phenotype - various disorders/diseases

What is a deletion and what are the consequences of this aberration?

Nondisjunction is the failure of chromosome pairs or sister chromatids to separate properly during cell division. This can result in aneuploidy which can lead to further problems such as Monosomy 21

What is chromosomal nondisjunction and how does it affect ploidy?

The major difference between aneuploidy and polyploidy is that polyploidy occurs due to altering the overall set of chromosome number to make it more than 2n, whereas aneuploidy occurs due to altering a particular chromosome or part of a chromosome such as 2n-1(monosomic).

What is the difference between aneuploidy and polyploidy?

If nondisjunction occurs during the first meiotic division, two trisomic individuals will arise and two monosomic individuals will arise. If this occurs during the second meiotic division, two normal (disomic) individuals will arise, one trisomic, and one monosomic. Individuals will end up with either a deficient number of chromosomes or an excess number of chromosomes

What is the difference between chromosomal disjunction errors during meiosis I and meiosis II and how does each affect the cell?

Inversions do not result in the loss or addition of genetic material whereas deletions/duplications do

What is the fundamental difference between deletions/duplications and inversions?

If only one of the genes in the homolog is represented by a lethal allele, monosomy results in unmasking of the recessive lethal allele that would usually be masked by the dominant allele present

What is the meaning of the statement 'autosomal monosomies unmask the lethal alleles'?

Susumu Ohno stated that genes and genomes are duplicated in evolution to protect essential genes and generate new genes through variation and adaptive mutations.

What is the role of duplications in evolution?

Nondisjunction during Anaphase II of Meiosis

What kind of mistake in cell division can lead to XYY aneuploidy?

A Robertsonian translocation is a type of reciprocal translocation where two acrocentric chromosomes fuse to form a new, large submetacentric or metacentric chromosome

What kind of translocation is called 'Robertsonian translocation'?

Reciprocal translocation between HSA9 and HSA22 ).

What type of translocations has generated the Philadelphia chromosome?

Allopolyploid Having more than two sets of chromosomes, resulting from mating between members of two different species. Autopolyploid Having more than two sets of chromosomes, resulting from mating between individuals of the same species.

What's the difference between Autoployploidy and Allopolyploidy?

Sex Chromosomes have a low number of genes on Y chromosome and can undergo X inactivation. The only reason there is an effect due to sex chromosome aberrations is due to genes that escape X inactivation and are not in PAR

Why are autosomal numerical aberrations less tolerated by the cell than aberrations in the number of sex chromosomes?

They can lead to mistakes in maternal meiosis, paternal meiosis, or mitotic errors during zygotic/embryonic development

Why do chromosomal aberrations lead to disease and disorders?

Because it would change gene dosage and expression

Why does polyploidy alter the organism's phenotype?

Larger chromosomes would cause greater genetic imbalance than smaller ones

Why is autosomal trisomy more tolerated when it happens in small chromosomes than when it happens in large chromosomes?

Because of the specifics of mammalian female meiosis due to which the age of oocytes passing through the first and the second meiotic divisions is the same as the age of the woman. Therefore, more mistakes occur in meiotic divisions of older oocytes in older women leading to aneuploidies.

Why is the probability of having children with autosomal trisomies increasing with maternal age?