Chromosomal Aberrations Chromosomes contain units

Chromosomal aberrationschanges in the chromosomes (mutations) Variations in the chromosome number
Aneuploidy
Addition or loss of one or more chromosomes
Trisomy (2N+1), monosomy (2N-1)
Polyploidy
Addition of chromosome sets
Triploidy (3N), tetraploidy (4N) Alterations in the chromosome structure
Deletion – loss of part of a chromosome
Duplication – segment of a chromosome is repeated
Inversion – part of a chromosome is oriented in the reverse of its usual direction
Reciprocal translocation – part of a chromosome breaks off and attaches to another, non-homologous chromosome<br>

Identify the type of alteration that has occurred.<br>

Aneuploidy in humans Trisomies in Autosomes
Trisomy 21: Down Syndrome (47, 21+)
Trisomy 18: Edwards Syndrome (47, 18+)
Trisomy 13: Patau Syndrome (47, 13+) Aneuploidy of Sex Chromosomes
Turner Syndrome (45, XO)
Klinefelter Syndrome (47, XXY)
Jacobs Syndrome (47, XYY)
Metafemale (47, XXX)<br>

Trisomy 21 (47, 21+): Down Syndrome

Most common single cause of birth defects in humans
1/660 births
Prominent facial features (upward slanting eyes, open mouth with tongue protrusion)
Simian crease in palm (one horizontal line only)
Mental retardation that ranges from mild to severe
Congenital heart defects
Increased susceptibility to many diseases
Mostly sterile
Shorter life span
Increased risk with older mothers<br>

Down Syndrome and Maternal Age Some studies also show the gene for Alzheimer’s disease is found in Chromosome 21; there may be a correlation with Down Syndrome<br>

Trisomy 18: Edwards Syndrome

Second most common autosomal trisomy after trisomy 21.
1/6000-8000 live births
Severely affects ALL organ systems
Approximately 95% of conceptions with trisomy 18 die in embryonic or fetal life; 5-10% of affected children survive beyond the first year of life.
The high mortality rate is usually due to the presence of cardiac and renal malformations, feeding difficulties, sepsis, and apnea caused by CNS defects.
Severe psychomotor and growth retardation are invariably present for those who survive beyond infancy.<br>

Trisomy 13: Patau Syndrome

1/5000 live births
Multiple abnormalities, many of which are not compatible with more than a few months of life.
Almost half of the affected infants do not survive beyond the first month, and about three quarters die within 6 months.
Severe mental defects and defects of the brain that lead to seizures, apnea, deafness, and eye abnormalities.
Most infants have a cleft lip and cleft palate, polydactyly and low-set ears. Congenital heart disease is present in approximately 80% of affected infants. Hernias and genital abnormalities are common.
Because of the severity of congenital defects, life-sustaining procedures are generally not attempted.<br>

Monosomy X (45, XO): TURNER SYNDROME

The only known viable monosomy in humans
1/2000 live female births (and 15% of spontaneous abortions)
Phenotypically female
Sterile, short stature, webbed neck, immature sex organs, secondary sexual characteristics fail to develop, “shield”-type chest (broad and flat)<br>

Klinefelter Syndrome: 47, XXY

Approximately 1 in 500-1,000 males is born with an extra sex chromosome;
About 40% of conceptions with Klinefelter syndrome survive the fetal period.
In general, severity of somatic malformations in Klinefelter syndrome is proportional to the number of additional X chromosomes; mental retardation and hypogonadism are more severe in 49,XXXXY than in 48,XXXY.
Mortality rate is not significantly higher than in healthy individuals. Tall stature – thin build and disproportionately long arms and legs Adolescent male with gynecomastia (slightly developed breasts) Adolescent male who has female-type distribution of pubic hair and underdeveloped testes.<br>

Jacobs / XYY Syndrome (47, XYY)

1/1000 births
Affected individuals are usually very tall and thin.
Many experience severe acne during adolescence.
Additional symptoms may include antisocial or behavioral problems and learning disabilities.
Intelligence is usually normal, although IQ, on average, is 10 to 15 points lower than siblings.<br>

Metafemale / XXX Syndrome

7.4-15.6/10,000 female births or 3.6-7.5/10,000 births
Fetal death rate is not notably higher than that for conceptions with normal chromosomes
The clinical features are subtle and can be variable.
Often not identified in infancy.
Minor birth defects include wide spaced eyes, wide spaced nipples, abnormally-sized head (either small or wide).
Typically have tall stature by adolescence and normal sexual development and puberty, are fertile, and have no or minor mental retardation but often have learning disabilities and may have problems with motor coordination.
Approximately 90% of cases are of maternal origin and 10% of paternal origin. Of the triple X syndrome cases of maternal origin, 70% result from nondisjunction in meiosis I, which increases with maternal age.<br>

Abnormal Chromosome Structure DELETION – a portion of a chromosome is lost during cell division; the chromosome from which the fragment originated will now be missing certain genes

Cri-du-chat Syndrome (deletion at 5p)
Deletion at short arm (p) of chromosome 5<br>

Cri-du-chat Syndrome Between 1 in 20,000 and 1 in 50,000 babies are affected
Infants with cri du chat syndrome commonly have a distinctive cat-like cry (malformation of larynx)
They also have an extensive grouping of abnormalities with severe mental retardation being the most important.
Small head, wide-set eyes, low birth rate, slow growth<br>

Abnormal Chromosome Structure DUPLICATION - the fragment that got cut off from one chromosome attaches to its homologue, thus duplicating certain genes on it
INVERSION - the fragment that got cut off from one chromosome is able to RE-ATTACH to it, but in the reverse orientation
TRANSLOCATION
- the fragment that got cut off from one chromosome attaches to another, non-homologous chromosome
- it may also be an exchange of fragments between two non-homologous chromosomes (reciprocal translocation)<br>

Translocation: The Philadelphia Chromosome


between one chromosome 9 and one chromosome 22. This translocation is designated t(9;22).
It results in one chromosome 9 longer than normal and one chromosome 22 shorter than normal. The latter is called the Philadelphia chromosome and designated Ph1.
causes chronic myelogenous leukemia
chromosome abnormality not found in any nonleukemic white blood cells, nor in any other cells of the patient's body<br>

Reciprocal translocation  t(9;22) The fusion of the two genes (red and green dots) in the Philadelphia chromosome is what eventually causes the leukemia.
This is because it forms a new protein that causes uncontrollable cell division of cells in the bone marrow that give rise to WBC.<br>

Robertsonian Translocation:
Down Syndrome Carrier – t(14;21)

A portion of, or an entire, chromosome 21 fuses with one chromosome #14.
Individual is phenotypically normal, but could have children with Down Syndrome (gametes may be produced that contain one # 21 and the abnormal # 14 (fused with 21); if fertilized, these would lead to Down Syndrome<br>

Tyler is a newborn baby suspected of having Down syndrome. Chromosome analysis reveals that he has three copies of chromosome 21, but the long arm of one chromosome 21 is translocated onto the long arm of one chromosome 14 at the centromere. Because chromosomes 14 and 21 are acrocentric chromosomes, Tyler is said to have a Robertsonian translocation. Chromosome analysis reveals that Tyler's father, Josh, has normal chromosomes, but Tyler's mother, Dawn, has 45 chromosomes, including a balanced 14;21 Robertsonian translocation.<br>