Large-Scale Chromosomal Changes and Their Significance
Large-Scale Chromosomal Changes
Chapter 17 focuses on the various chromosomal changes and their implications, including aneuploidy, structural rearrangements, and their effects on organisms. These changes can lead to significant phenotypic variations and genetic disorders.
Reciprocal Translocation
Reciprocal translocation occurs when segments from two different chromosomes break and re-attach to each other. This results in chromosomes that have traded segments, which can lead to abnormal meiosis due to unusual pairing of chromosomes. The phenomenon can cause genetic disorders if gametes are formed with unbalanced chromosome complements.
Down Syndrome
Down syndrome, also known as trisomy 21, is a genetic disorder that arises due to nondisjunction during gamete formation, resulting in an individual having three copies of chromosome 21. Symptoms include mental retardation (with an IQ generally between 20-50), physical features like a broad, flat face, short stature, short hands, and various heart defects. The disorder occurs in about 0.15% of all live births, with maternal age being a critical risk factor for nondisjunction events leading to this condition. Interestingly, females with Down syndrome can be fertile, while males are typically sterile.
Types of Chromosome Mutations
Understanding chromosome mutations is crucial for studying genetics. There are several types of mutations, including:
Euploidy: Describes an organism having an exact multiple of the haploid number of chromosomes. Polyploidy refers to having more than two sets of chromosomes (e.g., triploid is 3n, tetraploid is 4n).
Aneuploidy: Defects in chromosome number, where an individual has either more or fewer chromosomes than the wild type. The terms for variation in chromosome number include:
Trisomic (2n+1) : One extra chromosome
Monosomic (2n-1) : One missing chromosome
Nullisomic (2n-2) : Loss of both homologs of a chromosome.
Polyploids
Polyploidy is more common in plants than in animals and often promotes speciation. Polyploids are classified as:
Autopolyploids: Contain multiple chromosome sets from the same species (e.g., triploids, tetraploids).
Allopolyploids: Combinations of chromosome sets from different species; they must come from closely related species, which results in homeologous chromosomes.
For example, the hybridization of radish and cabbage produces a sterile individual. Still, through spontaneous genome duplication, a new fertile allopolyploid, Raphanobrassica, is formed.
Aneuploidy and Nondisjunction
Nondisjunction, which refers to the failure of homologous chromosomes to separate properly during cell division, is a primary cause of aneuploid conditions. It can lead to gametes with abnormal chromosome counts, resulting in offspring with various genetic disorders. Meiotic nondisjunction can occur in either the first or second division of meiosis, impacting the genetic balance in gametes.
Monosomics
Monosomics usually result in severe consequences, including spontaneous abortion. A notable example is Turner syndrome (XO) in females, characterized by short stature, sterility, and certain physical features with normal intelligence levels.
Gene-Dosage Effect
The gene-dosage effect illustrates how the number of gene copies influences mRNA production and subsequent protein synthesis.(Change the amount of MRNA you change the protein proportionally) An imbalance in this ratio can result in significant phenotypic abnormalities. In aneuploid organisms, this can lead to their increased abnormality compared to polyploids.
Dosage Compensation
sexchromosome are diffrent
They kind of cat like a natural monosomic
how do we preven gene dosage effect (inactivate the other chromosome in humans)
Are there other ways for this to happen (some upregulate the genes expression to compiste for the number of chromosomes they have)
Chromosome Structure and Rearrangements
1. Each chromosome is a single stranded DNA molecule
2. The first event in the reproduction of a chromosomal rearrangement is the generation of two or more double-stranded breaks in the chromosomes
3. Double-stranded breaks are potentially lethal unless repaired
4. Repair systems in the cell correct these breaks by joining the broken ends back together
5. If the two ends of the same break are rejoined the original DNA order is restored
6. If two different breaks are joined the result is a chromosomal rearrangement
7. For an organism to survive the rearrangement must have a single centromere and two telomeres
8. If rearrangement duplicates or deletes a segment of chromosome, gene balance may be affected
Nonallelic homologous recombination (NAHR)
• Another cause of rearrangements is crossing over between repetitive
DNA segments
• Unbalanced rearrangements change the dosage of the chromosome
segment by removing or duplicating DNA
• Balanced rearrangements change the gene order but do not remove
or duplicate any DNA
Deletions
• Deletions have many consequences
• The piece snipped out is still in the cell but has no centromere so it can’t be
dragged to the spindle in cell division and is lost
• Small deletions within a gene are called intragenic deletions
• They inactivate the gene and act just as any other null mutation
• Multigenic deletions involve the loss of several genes
• These types of deletions have more severe consequences
• Homozygosity of multigenic deletions is always lethal
• Depending on the segment lost, sometimes even heterozygotes don’t
survive (likely due to gene balance or exposure of recessive lethals)
Deletion hoops in drosophila
small deletion are somtiebs viable
when C and D are deleted in one chromosome then on the other chromosome it would form
a deletion bubble called a deletion loop
Chromosomal rearrangements, which include deletions (lost segment of a chromosome), duplications (insertion of a segment), inversions, and translocations, disrupt the normal balance of genetic material. Deletions can have severe consequences and are often lethal if multiple genes are lost, while duplications can lead to gene redundancy. Inversions change gene order but usually do not result in large-scale gene loss. Understanding these structural alterations is crucial for genetics and evolutionary biology.
Cri du chat Syndrome (result of a deletion)
One illustrative example of the consequences of chromosomal deletions is Cri du chat syndrome, which results from a deletion on chromosome 5 due to parental translocations. Those affected display distinct high-pitched cries, low birth weight, microcephaly, and intellectual disabilities, underscoring the impact of chromosomal integrity on development.
In summary, large-scale chromosomal changes can profoundly influence genetic stability and diversity, impacting evolutionary processes and contributing to various genetic disorders in humans and other organisms.
Williams syndrome (unqule crossing over) is another genetic disorder caused by a deletion, specifically on chromosome 7, which leads to a range of developmental issues, including distinct facial features, cardiovascular problems, and intellectual disabilities. This highlights the significance of chromosomal changes in shaping both physical and cognitive attributes in individuals.
• Caused by a 1.5 Mb deletion on
one homolog of chromosome 7
• This segment contains 17 genes
• The abnormal phenotype is
caused by haploinsufficiency of
1 or more of these genes
Duplication
mutation ofen lead to exre copies of a fine
duplicated region can be adjacent
the can also be located else where in the genome insertional duplication
diploid with duplication will have 3 copes
deletion tandem edubplciaion result in loops during prophase
inversion
paracentrin inversion: do not include centromere
paricentric inversion: do include
Reciple transolcation