Variation in Chromosome Structure and Number

Overview of Chromosomal Structural Changes

Chromosomal structure can be altered in several ways, affecting the amount or arrangement of genetic material. These changes are classified into two main categories:

• Changes in the total amount of genetic material: Includes deletions (loss of genetic material) and duplications (gain of extra copies).

• Rearrangements without changing the total amount: Includes inversions (a segment is flipped in orientation) and translocations (segments are exchanged or moved between non-homologous chromosomes).

Types of Chromosomal Structural Changes

• Deletion: Loss of a chromosome segment.

• Duplication: Repetition of a chromosome segment.

• Inversion: A segment is reversed within the chromosome.

• Simple Translocation: A segment moves from one chromosome to another.

• Reciprocal Translocation: Segments are exchanged between two non-homologous chromosomes.

Deletions and Duplications

Deletions

A chromosomal deletion occurs when a chromosome breaks and a fragment is lost. There are two main types:

• Terminal Deletion: Loss of a segment from the end of a chromosome.

• Interstitial Deletion: Loss of an internal segment, with the two outer pieces rejoining.

Phenotypic Consequences:

• Depend on the size and location of the deletion.

• Usually detrimental if they affect essential genes.

• Example: Cri-du-chat syndrome in humans is caused by a deletion on the short arm (p arm) of chromosome 5, leading to intellectual disability and a characteristic cry in infants.

Duplications

A chromosomal duplication is usually caused by abnormal recombination events, such as misalignment of repetitive sequences during meiosis, leading to non-allelic homologous recombination.

• Duplications can be tandem (adjacent) or displaced (separated by other sequences).

• Phenotypic effects are generally less severe than deletions of similar size.

• Large duplications are more likely to have phenotypic consequences.

• Duplications provide raw material for evolution, allowing the formation of gene families.

Example: The globin gene family in humans arose from repeated gene duplications, resulting in multiple related genes with specialized functions (e.g., myoglobin in muscle, hemoglobins in red blood cells).

Formation of Gene Families

• Duplicated genes can accumulate mutations and diverge in function.

• Related genes within a species are called paralogs.

• Gene families, such as the globin family, illustrate how duplications contribute to genetic diversity and specialization.

Copy Number Variation (CNV)

Copy Number Variation refers to segments of DNA that vary in copy number among individuals of a species.

• Common in both animals and plants; in humans, about 0.4% of the genome shows CNV.

• Produced by mechanisms such as non-allelic homologous recombination, transposable element proliferation, and replication errors.

• Associated with diseases like schizophrenia, autism, learning disabilities, susceptibility to infections, and cancer.

Inversions and Translocations

Inversions

An inversion occurs when a chromosome segment is flipped in orientation. There are two types:

• Pericentric Inversion: Includes the centromere.

• Paracentric Inversion: Does not include the centromere.

Consequences:

• Usually no change in the total amount of genetic material.

• Most inversions have no phenotypic effect, but can cause problems if break points disrupt important genes (break point effect) or alter gene regulation (position effect).

Inversion Heterozygotes

• Individuals with one normal and one inverted chromosome are called inversion heterozygotes.

• Usually phenotypically normal, but have a high probability of producing abnormal gametes due to crossing over within the inversion loop during meiosis I.

• Crossing over in a pericentric inversion produces chromatids with duplications and deletions.

• Crossing over in a paracentric inversion can produce an acentric fragment (lacking a centromere, lost during cell division) and a dicentric chromosome (with two centromeres, which breaks during anaphase).

Translocations

Types and Mechanisms

• Reciprocal Translocation: Exchange of segments between two non-homologous chromosomes. Can occur via chromosomal breakage and faulty repair or nonhomologous crossover.

• Balanced Translocation: No net gain or loss of genetic material.

• Unbalanced Translocation: Genetic material is duplicated in one location and deleted in another, often causing phenotypic abnormalities or lethality.

Example: Familial Down Syndrome is caused by a translocation between chromosomes 14 and 21, resulting in three copies of most chromosome 21 genes.

Robertsonian Translocation

• Occurs when breaks happen near the centromeres of two acrocentric chromosomes.

• The long arms fuse to form a single chromosome; the short arms are lost.

• Most common chromosomal rearrangement in humans.

• Carriers have increased risk of producing unbalanced gametes.

Meiotic Segregation in Translocation Heterozygotes

During meiosis I, individuals with reciprocal translocations form a translocation cross (quadrivalent) to allow homologous regions to pair. Three segregation patterns are possible:

• Alternate and adjacent-1 segregation occur at similar frequencies; adjacent-2 is rare.

• High frequency of unbalanced gametes leads to semisterility (reduced fertility).

Additional Examples (Not on Exam)

• Human Chromosome 2: Resulted from a Robertsonian translocation not present in other great apes, explaining differences in chromosome number between humans and apes.

• Chronic Myelogenous Leukemia: Caused by a reciprocal translocation between chromosomes 9 and 22, creating the BCR-ABL fusion gene, which drives unregulated cell division.

Key Terms:

• Deletion: Loss of a chromosome segment.

• Duplication: Repetition of a chromosome segment.

• Inversion: Reversal of a chromosome segment.

• Translocation: Movement of a segment to a different chromosome.

• Paralog: Homologous gene within a species, arising from duplication.

• Copy Number Variation (CNV): Variation in the number of copies of a particular DNA segment among individuals.

• Robertsonian Translocation: Fusion of two acrocentric chromosomes at their centromeres.

• Semisterility: Reduced fertility due to production of unbalanced gametes.

Summary Table: Types of Chromosomal Structural Changes

Additional info: The above notes expand on the original slides by providing definitions, examples, and summary tables for clarity and completeness.