5. chromosome and karyotype rearrangements

define aneuploidy and polyploidy. know the difference

aneuploidy: having abnormal number of chromosomes (missing or an extra), affects specific chromosomes, ex: monosomy (turner syndrome) or trisomy (down syndrome)

polyploidy: having more than 2n complete sets of chromosomes, affects all chromosomes, mostly in plants → bigger fruit/flowers

why are chromosomal aberrations leading to disease and disorders

they alter the genetic instructions for growth, development and cell function

why are autosomal numerical aberrations less tolerated by the cell/organism than aberrations in the number of sex chromosomes

autosomes carry many essential genes so extra/missing copies cause major imbalances

sex chromosomes are better tolerated because extra x chromosomes are largely inactivated and the y chromosome has fewer genes, meaning fewer essential functions are disrupted

what is chromosomal nondisjunction and how does it affect ploidy

failure of homologous chromosomes or sister chromatids to separate correctly during cell division which leads to daughter cells having too many/ few chromosomes, disrupting ploidy

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

meiosis I: ( homologous pairs fail to separate) affects all resulting gametes → more severe

meiosis II: (sister chromatids fail to separate) affects of the gametes → 2 normal, 2 abnormal

what are the usual consequences of meiotic errors

aneuploidy → genetic/structural disorders or miscarriage

what is the meaning of the statement “autosomal monosomes unmask lethal alleles”

the absence of 1 entire non-sex chromosome (autosome) exposes the harmful effects of a recessive lethal allele that would normally be masked by a functional allele on the homologous chromosome in a healthy individual

trisomy for many different chromosomes is routinely observed in spontaneous abortions (miscarriages) but monosomy isn’t, why

the embryo can still develop with trisomy but will typically miscarriage due to severity, however, monosomy prevents the embryo from developing altogether (monosomic zygotes die before implantation and there’s no recognized pregnancy)

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

essentially, it's less about chromosome size and more about the number and type of genes on the extra chromosome; small chromosomes (like 21, 18, and 13) happen to have fewer genes and are thus compatible with life, even if they cause significant problems

what are the 3 human chromosomes that can be trisomic in liveborns and which is the most common among them

trisomy 21 (down syndrome), trisomy 18 (Edwards syndrome), trisomy 13 (patau syndrome); trisomy 21 is most common

cite and explain 1 possible reason for the trisomy 21 disorder and name the syndrome

most common reason is an error in cell division called nondisjunction where the pair of chromosome 21 fail to separate properly during meiosis; the syndrome is down syndrome

miscarriages with trisomy of chromosome 1 or chromosome 19 are never seen, do they ever occur

yes they occur but are rare in miscarriages and live births because these large gene-dense chromosomes are so critical that embryonic survival is usually prevented

which germline events can lead to human polyploidy

1. Tetraploids: mitotic failure in embryogenesis, cell fusion (lethal)

2. Triploids: egg fertilized with two sperms, ovum fused with polar body and fertilized with haploid sperm, meiosis I or II errors in oogenesis or spermatogenesis.

true or false. cases of polyploidy are rare in mammals, birds and reptiles

false, it’s only rare in birds and mammals

what are the consequences of numerical aberrations in sex chromosomes for the organism

affected individual is usually viable, can lead to sub fertility or infertility and mild physical/mental problems

what kind of mistake in meiotic cell division can lead to xyy aneuploidy

failure of chromosomes to separate leading sperm with an extra y chromosome

which has a more severe effect of phenotype: deletion of the p arm of the X chromosome or deletion of the q arm

p arm because it’s closer to the centromere but both can also depend on the gene lost

name the main categories of structural aberrations that can occur in mammalian chromosomes

1. type of changes: deletions, duplications, inversions, translocations

2. type of cell: somatic aberrations (mitosis), germ cells (meiosis-inherited)

3. extent: both homologs (homozygous), one homolog (heterozygous)

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

loss of any genetic material (single locus or larger segments), mechanisms: chromosomal breaks (terminal- 1 break, inter arm- 2 breaks)

consequences: loss of chromosome segments, loss of gene(s) and gene products, problems in meiotic pairing, changes in phenotype (phenotypic variation, disorders/diseases)

in a pair of homologous chromosomes, one homolog has a deletion. what will happen in pachytene (when homologous chromosomes pair up)

the normal chromosome forms a loop to align with the shorter deleted homolog, allowing for synapsis and recombination

name the consequences of duplications

1. redundancy of genetic material (overdose)

2. problems in meiotic pairing

3. changes in phenotype (phenotypic variation, disorders/diseases)

what is the role of duplications in evolution and give an example

to protect essential genes (ribosomal RNA genes, developmental/immune system genes) and generate new ones (variation, adaptive mutations)

what are paralogous genes and give an example

genes in the same species as a result of gene duplications, share some sequence similarity but have distinct gene products and functions

ex: alpha, beta, gamma globins; milk caseins

what is the fundamental difference between deletions/duplications and inversions (hint: genome balance)

deletions/duplications change the total amount of genetic material, inversions only change the linear order (inverts 180 degrees) of genes

in which way do translocations differ from deletions/duplications/inversions (hint: think in terms of homologous and non-homologous chromosomes)

translocation involves the exchange or movement of material between non-homologous chromosomes, whereas the others involve structural changes within single chromosomes or homologous chromosomes

name the 2 main types of translocations (hint: type of exchange)

non-reciprocal, reciprocal, robertsonian (fusion of two acrocentric chromosomes (small arms lost, centromere is the end)

what type of translocation has generated the Philadelphia chromosome

(HSA9/22) reciprocal ranslocation describe the

describe the human Philadelphia chromosome and its homolog in dogs

human Philadelphia: chromosomes 9 and 22, fusion of BCR-ABL genes, result fusion protein: abnormal signal transduction and continuous proliferation (rapid increase in numbers) of cells, myeloid leukemia

dog Philadelphia (Raleigh chromosome): chromosomes 9 and 26, result fusion protein: abnormal cell regulation and cancer, myeloblastic leukemia

what are the possible consequences of translocations for reproduction

meiotic products are genetically unbalanced, lethality of gametes, partial monosomy or trisomy → birth defects

explain the difference between balanced and unbalanced gametes

balanced gametes: have complete but rearranged set of genetic material (no gain/loss), typically result in healthy individual

unbalanced gametes: have missing or extra DNA, typically result in miscarriage, infertility, or developmental disorders

what kind of translocation is called robertsonian translocation

the fusion of two acrocentric chromosomes (small arms lost, centromere is the end)

compare phenotypic consequences of deletion and inversions. which are more severe and why

deletion: phenotypic variation, disorders/diseases

inversions: affects homologous pairing and crossing-over in meiosis

give an example of a human genetic disorder associated with fragile sites. explain its molecular mechanism

fragile sites: heritable loci on chromosomes that are visible as gaps/breaks when cells are exposed to chemicals that inhibit DNA replication; common sites: found in all individuals and not associated with disease, rare sites: rare and associated with disease

fragile x syndrome is the expansion of trinucleotide repeats which leads to autism and intellectual disability. this condition worsens with each consecutive generation (genetic anticipation)

what are disorders of sex development, also known as sex reversal syndromes

disagreement between chromosomal and phenotypic sex (xx males, xy females)

males: SRY positive (80%)- SRY translocated to x, SRY negative- mutation in autosomal genes, phenotype: disorders of sexual development/ reproduction

females: SRY negative- deletion or mutation in SRY, SRY positive- mutations in x-linked or autosomal genes, phenotype: normal, tall, good looking, slim, sterile