CHROMOSOME ABNORMALITIES Flashcards
typical number of chromosomes in a human cell
46: 23 pairs
Types of Chromosomal Abnormalities
- Constitutional Abnormalities
- Acquired or Somatic Abnormalities
- Numerical Anomalies
- Structural Anomalies
Refers to anomalies that are inborn and have been always present in the embryo
Constitutional Abnormalities
Developed due to exposures, habits, or malignancies
Acquired or Somatic Abnormalities
- Happens when the number of chromosomes in a somatic cell is not 46
- If individual chromosomes have extra, missing, or rearranged genetic material
- Account for 50% of spontaneous abortions but only 0.65% of newborns are born with these abnormalities
Numerical Abnormalities
- Presence of extra sets of chromosomes
Polyploidy
an individual who has 3 sets or copies of chromosomes
Triploid (3N)
Causes of polyploidy
- 2/3 are because of fertilization of an oocyte by 2 sperms
- Other cases are because of a diploid gamete
Polyploidy is responsible for ?% of spontaneous abortions
17
- Either the sperm or the egg has two full sets of chromosomes, leading to a triploid baby
- Total chromosomes: 69
Triploid Syndrome
- Cells have a missing single chromosome or having an extra chromosome
- Literally translates as “not good set”
- Most are spontaneously aborted
- Those that survive have specific syndromes depending on which chromosomes are missing or extra
Aneuploidy
causes of aneuploidy
- Nondisjunction
- Anaphase lag
- Meiotic error where chromosome pair does not separate at anaphase of either the 1st or the 2nd meiotic division
- This unequal division produces a sperm or oocyte that has two copies of a particular chromosome, or none, rather than one copy
Nondisjunction
- Result of a delayed movement (lagging) during anaphase
- Chromosome in meiosis or a chromatid in mitosis that fails to migrate or connect to the pole of the spindle apparatus will be lost from the nucleus as division is completed
Anaphase Lag
missing chromosome
Hypoploidy
extra chromosome
Hyperploidy
- absence of one member of a pair of chromosomes
- 2n-1
Monosomy
- the loss of both pairs of homologous chromosomes
- 2n-2
Nullisomy
- chromosomal condition characterised by an additional
chromosome - 2n+1
Trisomy
- is a condition where there is more than one copy of the chromosome relative to the normal
- > 2n+1
Polysomy
- Most common autosomal aneuploid among liveborns
- Patients survive because Ch21 has the fewest genes
- Intelligence varies but developmental milestones come
- Common for babies born to elderly women
Down Syndrome or Trisomy 21
47, XY, +21
- Triple copies of chromosome 18
- Arise from nondisjunction in meiosis II
- Most patients have great physical and intellectual disability
- Skills remain stuck at 6 months level
- 90% of patients die within the first month
Edward’s Syndrome or Trisomy 18
47, XY, +18
- Kidney malformation
- Structural heart disease
- Omphalocele
- Esophageal atresia
- Cognitive delay
- Oddly clenched fist
- Rocker bottom foot
Characteristics of Edward’s Syndrome
- Triple copies of chromosome 13
- Not compatible with life
- Serious intellectual disability
- Great physical disability
- Most striking feature is the fusion of the developing eyes into one large eye-like structure in the center of the face
Patau Syndrome or Trisomy 13
47, XY, +13
- The most common trisomy in first-trimester losses.
- The diagnosis of a trisomy 16 conceptus will most likely result in a fetal loss in the first trimester.
- If mosaic trisomy 16 is present, the fetus may survive with near-normal developmental outcomes depending on the presence and degree of malformations.
Trisomy 16
- People with sex chromosome aneuploidy have extra or missing sex chromosomes.
- Some conditions can result from nondisjunction in meiosis in the male or female.
- Sex chromosome aneuploids are generally associated with much less severe symptoms and characteristics than autosomal aneuploids
Sex Chromosomes Aneuploidy
- Tall stature
- Delayed development of speech and language skills
- Hypotonia
- Curved pinky fingers (clinodactyly)
- Behavior and mental health problems
- Premature ovarian failure or ovary abnormalities
- Constipation or abdominal pains
Triple X Syndrome
- Monosomy of the X chromosome
- Generally, a sporadic event and the paternal sex chromosome is the most likely one missing
- X lang ang chromosome niya
- Features:
– Short stature
– Webbing at back of neck
– Incomplete sexual development (infertile)
– Impaired hearing
Turner (XO) Syndrome
treatment for Turner Syndrome
estrogen hormone therapy
- Karyotype: 47, XXY
- Estimated to affect 1:500 males
- The most common genetic or chromosomal cause of male infertility.
- Maybe identified as an incidental finding or may present with behavioral difficulties or as infertility in an adult.
- Technically a male with feminine features
Klinefelter’s (XXY) Syndrome
Features include:
– Incomplete sexual development
– Rudimentary testes and prostate
– Long limbs, large hands and feet
– Some breast tissue development
Klinefelter’s (XXY) Syndrome
treatment for Klinefelter
Testosterone therapy
- occur due to:
– It may have too much or too little genetic material
– It may have a stretch of DNA that is inverted or moved and inserted into a different type of chromosome
Structural Abnormalities
Structurally abnormal chromosomes can be:
- Balanced
- Unbalanced
– if they have the normal amount of genetic material
– Not usually any clinical significance for the patient, unless genes are disrupted, but may have consequence for offspring.
Balanced Structural Abnormality
– if they have extra or missing DNA sequences
– Due to gain or loss of normal complement of genetic material
Unbalanced Structural Abnormality
In some cells, the chromosome can break:
– Triggered by damage to DNA (radiation or chemicals)
– Part of recombination
If breaks occur at G1 Phase
if not repaired at S phase, affect both chromatids
If breaks occur at G2 Phase
affecting only one of the 2 sister chromatids
Recognize and repair broken chromosomes ends
Enzymes
Prevent cells with unrepaired chromosome breaks from entering mitosis
Cell Cycle Checkpoint Mechanism
- Occurs when a portion of the chromosome has broken off turned upside down and reattached
- The genetic material is inverted
- No loss or gain of chromosomal material thus carriers are normal
Inversion
- If the inverted segment is on the long or short arm and does not involve the centromere
- Inversion is on one side
Paracentric Inversion
- Breaks occur in both the short and long arms and the inverted segment contains the centromere
- Even the position of the centromere is moved
Pericentric Inversion
- An extra chromosomal segment within the same homologous chromosome or another nonhomologous chromosome
- CROSS OVER between misaligned chromosomes
- Chromosomal imbalance due to parental translocation or inversion
- Often not inherited; rather they arise de novo
- Effect on the phenotype is generally dependent on their size
Duplication
- May be caused by duplication of the gene encoding Peripheral Myelin Protein 22 (PMP 22) on chromosome 17
- Overexpression of PMP 22
- Manifestations:
– High foot arches
– Weakness of leg muscles
– Decrease sensation of legs
Charcot-Marie-Tooth Disease Type 1A
- Refers to the loss of a segment of a chromosome
- Often not inherited; rather they arise de novo
- Larger deletions increase the likelihood that there will be an associated phenotype
- Chromosomal breakage and loss of fragments can either be terminal or interstitial
- Unequal crossing over between misaligned homologous chromosomes or sister chromatids
Deletion
- Deletion 5p- (p arm of the 5th chromosome)
- Cry of cat syndrome
Cri-Du-Chat Syndrome
minute deletion of chromosome
microdeletions
the end part of the chromosome gets deleted
terminal
the center part of the chromosome gets deleted
interstitial
- Rare, formed when the 2 arms have fused together to form a ring
- More likely to be caused by the deletion of genes in the telomere regions of affected chromosome and the sticky chromosome ends fuse
- Genes can be lost or disrupted causing symptoms
Ring
Associated with mental retardation, dysmorphic facial features
Ring Chr 14 & Ring Chr 13
Associated with mental retardation, dwarfism & microcephaly
Ring Chr 15
– Associated with epilepsy
Ring Chr 20 Syndrome
Ring X Chromosome
Causes Turner Syndrome
- Is a structural rearrangement involving 2 non-homologous chromosomes
- Two nonhomologous chromosomes exchange segments
- Eg. Chromosome 1 & Chromosome 4
Translocation
- When segments from 2 different chromosomes have been exchanged
- If translocation breakpoint interrupts a gene, there may be an associated phenotype
Reciprocal Translocation
- A particular type of translocation
- Involves reciprocal transfer of the long arms of 2 of the Acrocentric Chromosome 13,14,15,21 or 22
- Acrocentric chromosomes break at the centromere and their long arms fuse
- Eg. Between Chromosome 14 & 21
Robertsonian Translocation
- Rare condition where chromosomes have identical short and long arms
- Formed when centromeres divide along the incorrect plane during meiosis
- These are formed when a chromosome has lost one of its arms and this arm is replaced with an exact copy of a chromosome segment including the centromere
- Seen in Turner Syndrome & tumor cells
Isochromosome
