Structural Chromosomal Abnormalities (LEC)

What is a balanced translocation?

A balanced translocation involves no gain or loss of genetic material, meaning the total amount of genetic material remains the same.

What is an unbalanced translocation?

An unbalanced translocation results in a gain or loss of genetic material, leading to genetic imbalances.

What is a reciprocal translocation?

A reciprocal translocation is an exchange of genetic material between non-homologous chromosomes.

How can a reciprocal translocation create a fusion gene?

In a reciprocal translocation, such as t(9;22) which leads to chronic myelogenous leukemia (CML), genetic material is exchanged, which can activate an oncogene and create a fusion gene that encodes a tyrosine kinase (like BCR-ABL) that contributes to cancer.

What is the Philadelphia chromosome?

The Philadelphia chromosome is a specific genetic abnormality in which a fusion gene created by a translocation between chromosomes 9 and 22 activates the BCR-ABL oncogene, leading to the development of chronic myelogenous leukemia.

What is a Robertsonian translocation?

A Robertsonian translocation occurs between acrocentric chromosomes, resulting in the loss of the short arms of the two chromosomes and a fusion of the long arms.

How can Robertsonian translocation explain Down syndrome?

In Down syndrome, a Robertsonian translocation can occur between chromosome 21 and another acrocentric chromosome (like chromosome 14 or 15), which can result in an extra copy of chromosome 21 material, leading to the condition known as trisomy 21.

What is the risk for a carrier of a Robertsonian translocation having a child with Down syndrome?

A carrier of a Robertsonian translocation involving chromosome 21 has a higher risk of having a child with Down syndrome, with the risk varying based on the specific translocation but can be significantly increased compared to the general population.

What is Cri-du-chat syndrome?

Cri-du-chat syndrome is caused by a deletion of chromosome 5, specifically 46, XX, del(5)(p15.3)(pter) or 46, XY, del(5)(p15.3)(pter). Symptoms include a high-pitched, cat-like cry, micrognathia, intellectual disabilities, microcephaly, and hypertelorism.

What is 22q11.2 deletion syndrome?

22q11.2 deletion syndrome results from a microdeletion on chromosome 22q11.2. It is associated with congenital heart defects, absence of the thymus (thymic aplasia), cleft lip/palate, learning disabilities, facial abnormalities, and an increased risk for schizophrenia.

What are the key features of Wolf-Hirschhorn syndrome?

Wolf-Hirschhorn syndrome is caused by a deletion of chromosome 4p. Symptoms include seizures, skeletal abnormalities, congenital heart defects, a spectrum of intellectual and developmental delays, and facial abnormalities.

What causes Prader-Willi syndrome?

Prader-Willi syndrome is due to a deletion of the paternal chromosome 15q11-13, which includes the SNRPN gene. It manifests as an eating disorder, developmental delay, hypotonia, hypogonadism, and distinctive facial features.

What are the characteristics of Angelman syndrome?

Angelman syndrome is caused by a deletion of the maternal chromosome 15q11-13, including the UBE3A gene. Symptoms include unprovoked laughing and smiling, jerky uncoordinated movements, lack of speech, hypotonia, and severe developmental delay.

What are inversions in chromosomes?

Inversions can be pericentric (involving the centromere) or paracentric (not involving the centromere). They are usually balanced and do not cause clinical problems in carriers. Inversions typically result in a change in the banding pattern of the chromosome and can be identified by karyotype analysis.

What are ring chromosomes?

A ring chromosome forms when a chromosome loses genetic material at its terminal portions, with the ends fusing to form a ring-like structure.

What is uniparental disomy?

Uniparental disomy is the inheritance of both chromosomes from the same parent, for example, chromosomes 15 as seen in Prader-Willi and Angelman syndromes. It may occur via a trisomy rescue mechanism, where non-disjunction during gamete formation results in a trisomic fertilization, and the zygote corrects this by ejecting one of the excess chromosomes. It can also happen if a fertilized embryo is monosomic, resulting in a single chromosome being duplicated to recreate the diploid state.

What are isochromosomes?

Isochromosomes occur when there is a loss of one arm of a chromosome and a duplication of the other arm. For instance, in females with Turner Syndrome, the long arms of the X-chromosome join to form an isochromosome. This typically results in chromosomal and gene dosage imbalance, and isochromosomes of autosomes are usually lethal, although they may be tolerated if present in a mosaic form.

What is Karyotype analysis?

Karyotype analysis is a cytogenetic test analyzed by microscopy that identifies relatively large chromosomal alterations. The banding pattern must be altered to detect deletions, duplications, inversions, translocations, and other abnormalities. It can typically visualize deletions larger than 5 Mb, while smaller deletions that are not visible are known as microdeletions.

What is FISH (Fluorescence In Situ Hybridization)?

FISH uses large probes (0.1 Mb or bigger) to detect chromosomal aberrations, including deletions, translocations, and gene amplifications, which is significant in cancer characterization. FISH provides a higher resolution than G-banded karyotypes, allowing for the detection of many microdeletions as long as they are larger than the probe being used.

What is Microarray CGH (Comparative Genomic Hybridization)?

Microarray CGH involves mixing patient DNA with normal control DNA, both labeled with different fluorescent dyes. This high-density method uses nearly a million probes, allowing for the detection of deletion or duplication mutations at a resolution far greater than conventional karyotype analysis. Each spot on the array corresponds to a specific position in the genome, enabling comprehensive analysis of chromosomal variations.