Changes in Chromosome Structure

Chromosome Structure Mutations Description Duplication Portion of the chromosome has been doubled Deletion Loss of chromosome segment Inversion A chromosomal segment is reversed (rotated 180o) Translocation A chromosomal segment is moved to another non-homologous chromosome

Mechanisms of Chromosome Mutation Breakage and Rejoining Unequal crossing-over

Duplications Type of Duplication Description/Example Adjacent-Tandem Duplicated region is immediately adjacent to the original segment A B C B C D Adjacent-Reverse Duplicated region is adjacent but the sequence is reversed A B C C B D Displaced Duplication is located on a different part of the chromosome or on a different chromosome.

Meiotic Structures Type of Mutation Meiotic Structure in heterozygotes Duplication Duplication Loop (Duplicated homolog forms loop, or both chromosomes form loops )

Consequences of Duplications Altered phenotypes as a result of imbalances in amounts of gene products

Consequences of Duplications Duplication can lead to other genetic changes Alleles with new functions

Consequences of Duplications Duplication can lead to other genetic changes Higher degrees of duplication

Deletions Type of Deletion Description Terminal Interstitial Loss of the end of a chromosome Interstitial Loss of internal portion of chromosome Intragenic Deletion within a gene, acts like a null mutation Multigenic Deletion of multiple genes, often harmful even in heterozygous condition

Meiotic Structures Type of Mutation Meiotic Structure in heterozygotes Deletion Deletion Loop (Normal homolog forms loop)

Consequences of Deletions Chromosome is lost if centromere is deleted. Chromosomes with deletions do not revert to the wild type state. Recombination frequencies between genes flanking the deletion are reduced. Deletions are lethal in the homozygous state.

Consequences of Deletions 5. Multiple defects occur in heterozygotes due to imbalances in the amounts of gene products Cri du chat syndrome results from a deletion in chromosome 5 Solid tumors can accumulate deletions

Consequences of Deletions 5. Multiple defects occur in heterozygotes due to pseudodominance = recessive alleles on the non-deleted homolog are expressed haploinsufficiency = certain genes must be present in two copies for normal function Wild Type Wing Notch Wing

Inversions Type of Inversion Description Paracentric Pericentric Centromere is outside inversion Pericentric Centromere is within inversion

Meiotic Structures Type of Mutation Meiotic Structure in heterozygotes Inversion Inversion Loop (Both homologs form loop)

Consequences of Inversions Generally viable since amount of genetic material is unchanged. Leads to lethal mutation if breakpoint is within an essential gene.

Consequences of Inversions Position Effect = Gene regulation can be altered by a difference in chromosome location Recombination frequency is reduced due to inhibition of pairing and since crossover in heterozygotes yields additional structural mutations.

Crossing Over in a Paracentric Inversion Heterozygote

Crossing Over in a Pericentric Inversion Heterozygote Anaphase II

Crossing Over in Inversion Heterozygotes Type of Inversion Crossover products Paracentric Dicentric bridge – breakage causes deletions Acentric fragment – lost Pericentric Chromosomes with both duplications and deletions

Inversions in Evolutionary History

Translocations Type of Translocation Description Reciprocal Exchange of chromosomal segments between non-homologous chromosomes Non-reciprocal Segment from one chromosome joins a non-homologous chromosome

Robertsonian Translocation Long arms of two acrocentric chromosomes are joined to the same centromere Results in one large chromosome and one small chromosome Smaller chromosome may be lost

Inheritance of Down Syndrome from the carrier of a Robertsonian translocation, joining the long arms of chromosomes 14 and 21.

Consequences of Translocations Behave as point mutations if the breakpoint disrupts an essential gene. Show new linkage arrangements. Position Effect = Gene expression is altered as a result of the new environment for translocated material. Burkitt’s lymphoma is caused by a position effect.

Consequences of Translocations Position-effect variegation of eye color in fruit flies due to translocation of w+ next to heterochromatin

Translocations found in cells of solid tumors

Consequences of Translocations Leads to semisterility, where approximately half of the gametes carry structural mutations. Meiotic Structures Type of Mutation Meiotic Structure in heterozygotes Translocation Cross (Involves both homologs)

Meiotic Segregation in Translocation Heterozygotes

Meiotic Segregation in Translocation Heterozygotes