Cytogenetics 10/28 & 10/30: Structural Chromosome Abnormalities & Chromosomal Disorders

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

Chromosome Deletion, 2 causes and 3 examples of syndromes causes by chromosome deletions

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 

Translocation and the 2 types

An example of a structural chromosome abnormality - the movement of a chromosomal segment to a new location in the genome.

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 

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

46,XY,del(5p)(pter)

Cri-du-chat syndrome

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

46,XX,del(22(q11))

46,XY,del(22(q11))

DiGeorge Syndrome

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

Inversion and the 2 types

Chromosome structural abnormality: inversions

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

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

2. 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 and the 3 common-known chromosomes affected

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

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 and leave sticky ends that adhere together, leading to gene disruption.

Ring chromosome 20 causes seizures 

Mosaicism

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

Starts with a single fertilized egg, that develops errors in cell division during development. The earlier in development the error, the more severe the outcome.

Examples

• Mosaic Down syndrome

• Mosaic Klinefelter syndrome

• Mosaic tuner syndrome

Robertsonian Translocation

Robertsonian translocations are unique types of whole-arm translocations. 

two acrocentric (long arms fuse, loses short stubby arms) chromosomes fuse at the centromere, causing a REDUCTION in the chromosome number to 45, but usually do not cause phenotypic effects

This can lead to aneuploidy or balanced carriers.

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

• Down syndrome 

• Patau 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.

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

examples of autosomal trisomy and sex chromosomal trisomy

a type of Numeric abnormality, aneuploidy. A condition where an individual has an extra copy of a chromosome, leading to genetic disorders. (2n+1)

Autosomal trisomy:

• Edward’s Syndrome (47, XY, +18)

• Down Syndrome (47, XY, +21)

• Patau’s Syndrome (47, XX, +13)

Sex chromosome trisomy:

• Trisomy X (47, XXX)

• Klinefelter Syndrome (47, XXY)

• Jacob’s Syndome (47, XYY)

Monosomy

A type of numeric abnormality, aneuploidy. A condition where an individual is missing one copy of a chromosome. (2n-1)

Autosomal: LETHAL ☠

• rare cases individuals survive usually occur in cases of Partial monosomy (only a part of the chromosome is missing) OR mosaicism (where some cells are missing the chromosome, some cells have the chromosome)

Sex chromosome: Turner Syndrome (45,X) (2n-1)

Haploinsufficiency

A dosage effect of chromosome abnormalities.

The phenomenon where a single functional copy of a gene is insufficient to maintain a normal phenotype. Occurs when one copy of a gene is inactivated or deleted.

Dosage = 1, one copy deletion.

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.

2 outcomes of 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

   1. deletion and/or

   2. duplication of genetic material. Deletion due to unequal crossing over between misaligned homologous chromosomes

Examples

Thalassemias - a group of inherited hemoglobin disorders and the most common human single-gene disorder

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 the 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 

Chromosome abnormalities - the 4 Structural abnormalities and their subgroups

1. Deletion

   1. Breakage

   2. Unequal crossover

      1. Balanced

      2. Unequal=deletion/duplication

2. Duplication

   1. Unequal crossover

3. Inversion

   1. Paracentric

   2. Pericentric

4. Translocation

   1. Recipricol

   2. Robertsonian

2 types of chromosomal deletions due to Breakage

1. Terminal deletion

2. Interstitial deletion 

The outcome of deletions depend on their size (the phenotype depends on the genotype)

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, del(5p) (pter) or 46, XY, del(5p) (pter)

DiGeorge Sydrome 46, XY, del(22((q11) or 46,XX,del(22((q11) 

Prayer-Willi Syndrome (PWS inherited deletion from father) and Angelman Syndrome (inherited deletion from mother); both conditions result from chromosome 15 long arm deletion. 

Alpha Thalassemia

A genetic blood disorder characterized by reduced production of hemoglobin due to deletions or mutations affecting the alpha-globin gene cluster on chromosome 16. This can lead to anemia and other related health issues.

Normal - 4 functional genes

a-thalassemia trait; 2 functional a-genes, homozygous or heterozygous

HbH disease - 1 functional a-gene

Hb Bart’s Hydrops Fetalis Syngdrome - Lethal, 0 functional a-genes

2 Translocation types

translocation is a type of structural abnormality.

1. Reciprocal translocation: (46,XY, t(3;6) (p13;p22)) happens when breaks occur in two different chromosomes and the material is mutually exchanged. Total chromosome number is unchanged (46). No genetic information gained/lost. The resulting chromosomes are called derivative. No physical phenotype but spontaneous abortions and abnormal offspring.

2. Robertsonian Translocation: (45,XX, t(14q;21q)) are unique types of whole-arm translocations. Involves any two acrocentric chromosomes and results from the centric fusion of the long arms of these two chromosomes. Reduction in the number of chromosomes by 1, loss of the short arms. Generally no phenotype but abnormal reproduction.