Cytogenetics: Structural Chromosome Abnormalities & Chromosomal Disorders

These flashcards cover key vocabulary terms related to cytogenetics, focusing on structural chromosome abnormalities and chromosomal disorders.

Chromosome Deletion

A chromosomal abnormality in which a portion of chromatin from a single chromosome is lost.

1. A deletion occurs when a chromosome loses a segment because of a breakage

2. It occurs due to unequal crossing over

Deletions may be inherited from a carrier parent or may occur as de novo rearrangement

Most of the detectable and severe cases were identified as de novo cases. The deletion occurs during gamete formation

Examples of chromosomal deletions

Cri-du-chat syndrome: 46, XX(XY), del(5p) (pter)

DiGeorge syndrome: 46, XY(XX), del(22((q11)

Prader-Willi syndrome and Angelman syndrome, both deletions of chromosome 15 long-arm.

When the deletion is inherited from the father - Prader-Willi (PWS) syndrome 

When the same deletion is inherited from mother - Angelman syndrome 

Aneuploidy

A chromosomal mutation that results in an abnormal number of chromosomes.

Translocation

The movement of a chromosomal segment to a new location in the genome.

Translocation involves two non-homologous chromosomes in which an exchange of chromosomal material between the two non-homologous chromosomes occurs. 

Balanced translocations are very common

Two types of translocations 

1. Reciprocal translocation

2. Robertsonian translocation 

Cri-du-chat Syndrome

46, XX( orXY), del(5p)

A deletion at the terminal part of the short arm of chromosome 5, leading to severe mental retardation and specific facial defects.

DiGeorge Syndrome

Results from a chromosomal deletion in chromosome 22, causing craniofacial anomalies and heart defects.

Inversion

Intra-chromosomal structural rearrangement where the genetic segment is turned around 180 degrees within a chromosome.

Inversions do not involve a loss of genetic information but involve the rearrangement of the linear gene sequence

An inversion requires two breaks along the length of the chromosome and subsequent reinsertion of the inverted segment

The size of the inverted segment may be short or long, and the inverted segment may or may not include the centromere

Paracentric inversion: the 2 breaks are in one arm, doesn’t include the centromere 

Pericentric inversion: the 2 breaks spanned the 2 arms and it includes the centromere  

Inversions can be de novo, or passed from parents to offspring. Carrier will have reproductive problems, can be traced to meiosis 

Isochromosome

A chromosome with identical arms caused by misdivision of sister chromatids. Due to meiotic error and forming an abnormal gamete or postzygotic error

Isochromosomes are known for chromosomes 12, 21 and 17

It is a common cause of tumors

Ring Chromosome

Chromosomes shaped like rings that may arise when telomeres are lost, leading to gene disruption.

Ring chromosome 20 causes seizures 

Mosaicism

The presence of two or more genetically different cell lines in the same individual.

Robertsonian Translocation

Robertsonian translocations are unique types of whole-arm translocations. 

It involves any two acrocentric chromosomes and results from teh centric fusion of the long arms of these two chromosomes , while the short arms are usually lost. This can lead to aneuploidy or balanced carriers.

Carrier individuals will not generally show any physical phenotypic effects until reproduction example translocation Down syndrome 

Common Robertsonian translocation between chromosomes 13;14, and between 14;21

Balanced Translocation

A chromosomal rearrangement that preserves the total amount of genetic material.

Polyploidy

Having more than two complete sets of chromosomes.

Gametes

Reproductive cells that carry half the genetic material required to form a new organism.

Non-disjunction

The failure of chromosomes to separate properly during cell division, leading to aneuploidy.

Trisomy

A condition where an individual has an extra copy of a chromosome, leading to genetic disorders.

Monosomy

A condition where an individual is missing one copy of a chromosome.

Haploinsufficiency

The phenomenon where a single functional copy of a gene is insufficient to maintain a normal phenotype.

Cytogenetics

The branch of genetics that studies the structure and function of the cell, especially the chromosomes.

Mitosis

The process of cell division that results in two genetically identical daughter cells.

Meiosis

The process of cell division that reduces the chromosome number by half, resulting in gametes.

Chromosome deletion due to unequal crossing over

1. Balanced: chromosomal rearrangement with the correct amount of genetic material in a cell. Genetic material is in a different chromosomal arrangement, but it is in the correct amount and functioning properly, and often does not produce serious health consequences.

2. Unequal: Chromosomal rearrangement with a deletion and/or duplication of genetic material. Deletion due to unequal crossing over between misaligned homologous chromosomes

Thalassemias

Thalassemias are inherited blood disorders that result in reduced or absent production of either alpha or beta globin chains, causing varying degrees of anemia and related health issues.

The most common human single-gene disorders

Normally, equal amounts of alpha and beta globin chains are produced to make hb molecules with two alpha chains and two beta chains. Genetic mutations that affect the production of teh globin chains can lead to imbalance in the ration of the alpha-beta chains causing this inherited chronic anemia, thalassemia

Alpha-thalassemia - reduced number of alpha chain and increased number of beta-chain

Reciprocal translocation

Happens when breaks occur in two different chromosomes and the material is mutually exchanged

The total chromosome number is unchanged (46)

No genetic information is gained or lost in the exchange, but genes are moved to new chromosomal locations

The resulting chromosomes are called derivative 

Carrier individuals will not generally show any physical phenotypic effects 

Carriers may show reproductive abnormalities, infertility, spontaneous abortions and abnormal offspring