ch6 chromosomal aberrations

Copyright © 2009 Pearson Education, Inc.

6.0 Chromosomal Aberrations

Prepared by Pratheep Sandrasaigaran


By the end of this chapter you should be able to:

• Understand the meaning of Chromosomal aberrations.

• Abnormalities in chromosome• Numerical• Structural• Disorders


Diagram adopted from Internet Sources


6.1 Introduction



• What is meant by chromosomal abnormality?

•Additional of genetic material or whole chromosome.•Part of or a whole chromosome has been missing.•Defective formation of a chromosome.

• Increases or decreases in genetic material affect the normal development and function.

Chromosomal abnormalities


Copyright © 2009 Pearson Education, Inc.Prepared by Pratheep Sandrasaigaran

Two Chromosomal abnormalities

Adopted from Human Genetics concepts and Application 9th ed.

• Abnormal Chromosome Number

• Abnormal Chromosome Structure


6.2 Abnormal ChromosomeNumber



TECHNOLOGY

• What is the total chromosome found in your cells?

• A human karyotype is said abnormal if the number of chromosomes in a somatic cell is not 46.

• Abnormal chromosomes account for at least 50% of spontaneous abortions.

• Yet only 0.65% of newborns have abnormal chromosomes.

Abnormal ChromosomeNumber



Schematic presentation


Euploid

Autosomal Aneuploidy

Sex Chromosome Aneuploidy

Aneuploidy


Polyploidy

Triploid

Tetraploid

Octaploid

• Sex chromosome aneuploidy is less severe than autosomal aneuploidy.


• A cell with an entire extra sets of chromosomes.

• An individual whose cells have three copies of each chromosome is a triploid 3N. How?

• Mostly result from fertilization of an oocyte by two sperm, or.

• Diploid gamete (When a normal haploid sperm fertilizes a diploid oocyte).

Polyploidy



• Triploids account for 17 percent of spontaneous abortions and 3 percent of stillbirths and newborn deaths.

• Polyploids are very common among flowering plants, including roses, cotton, barley, wheat, and in some insects.

• Fish farmers raise triploid salmon, which cannot breed.

• Can you see more then a triploid?• The liver, for example, has some

tetraploid (4N) and even octaploid (8N) cells.

Polyploidy




• Cells missing a single chromosome or having an extra one due to defective meiosis in a parent.

• Rarely, aneuploids can have more than one missing or extra chromosome.

• Most autosomal aneuploids (with a missing or extra non-sex chromosome) are spontaneously aborted while Sex chromosome aneuploidy usually produces milder symptoms.

• Those that survive have specific syndromes depending upon which chromosomes in matter.

Aneuploidy



• Children mostly born with extra chromosome (trisomy) rather than a missing one (monosomy).

• Monosomies are so severe that an affected embryo ceases developing.

• The meiotic error that causes aneuploidy is called nondisjunction; chromosome pair fails to separate at anaphase of either the 1st or 2nd meiotic division.

Aneuploidy- Trisomy




sperm or oocyte


• What happens when such a gamete fuses with its partner at fertilization?

• The zygotes will have either 45 or 47 chromosomes, instead of the normal 46.

• Out of 49 possible aneuploidy, only nine types of aneuploids are recognized in newborns.

Aneuploidy



• Abnormal oocytes mostly have extra or missing chromosomes.

• Abnormal sperm often have structural variants, such as inversions or translocations.

• Most of the 50 percent of spontaneous abortions is due to:• Triploids• Trisomy 16• 45,X individuals (missing an X chromosome)

• dac

Chances of chromosome abnormalities- rare



• About 9 percent of spontaneous abortions happen due to:• Trisomy 13• Trisomy 18• Trisomy 21

• More than 95 percent of newborns with abnormal chromosome numbers have an extra or missing X or Y chromosome.

• Chromosome abnormalities- all together make 0.1 percent of all children. But nondisjunction occurs in 5 percent of recognized pregnancies.

Chances of chromosome abnormalities- rare



TEST YOUR KNOWLEDGE 1



1. Distinguish among a euploid, aneuploid, and polyploid

2. What happens during meiosis to produce:

a. an aneuploid

b. Polyploid


Autosomal Aneuploidy

Sex Chromosome Aneuploidy

Aneuploidy


Polyploidy

Triploid

Tetraploid

Octaploid


6.2.1 Autosomal Aneuploidy



• Chromosomes 21, 18, and 13….Why?

• These chromosomes carry far fewer protein-encoding genes than the other autosomes, compared to their total amount of DNA.

• Therefore, extra copies of these chromosomes are tolerated.

Common Trisomies




• Most common autosomal aneuploidy.

• Many people with Down syndrome have physical problems:• Heart and kidney defects• Hearing and vision loss.• A suppressed immune system can make influenza

deadly.• Digestive system blockages are common and may

require surgical correction

a. Trisomy 21- Down syndrome



• Chances of Trisomy 21 Down syndrome increases with the age of the mother.

• About 90 percent of trisomy 21 conceptions are due to nondisjunction during meiosis I in the female.

• The 10 percent of cases due to the male result from nondisjunction during meiosis I or II.

• The chance that trisomy 21 will recur in a family is 1%.

a. Trisomy 21- Down syndrome




• Edward syndrome have great physical and mental disabilities, with developmental skills usually stalled at the 6-month level.

• Major abnormalities include heart defects, a displaced liver, growth retardation, and oddly clenched fists, abnormally shaped and low-set ears, a small mouth and face, unusual or absent fingerprints.

• Most cases of trisomy 18 are traced to nondisjunction in meiosis II of the oocyte.

b. Trisomy 18- Edwardsyndrome




• About 92 percent of infants born with an extra chromosome 13 do not live to see their first birthdays

• Most striking is a fusion of the developing eyes, so that a fetus has one large eyelike structure in the center of the face.

• Major abnormalities affect the heart, kidneys, brain, face, and limbs. The nose is often malformed, and cleft lip and/or palate is present in a small head.

• There may be extra fingers and toes.

c. Trisomy 13- Patau syndrome



• Hypothesis 1: Older a woman is susceptible for longer oocytes arrested to complete meiosis (15 to 45 years) due to exposure to toxins, viruses, and radiation.

• Hypothesis 2: Females have a pool of immature aneuploid oocytes resulting from spindle abnormalities that cause nondisjunction. The abnormal oocytes remain to be released at later age.

• Hypothesis 3: Trisomies result from gametes in which a homolog pair do not extensively cross over during meiosis I and suppose to migrate to the same pole, packaging an extra chromosome into a gamete.

Why trisomy at late pregnancy



Name the syndrome below.


• Trisomy 21

• Heart and kidney defects

• Hearing and vision loss.

• Digestive system blockages are common and may require surgical correction.

Down syndrome





• Trisomy 13

• Fusion of the developing eyes.

• There may be extra fingers and toes.

Patau syndrome





• Trisomy 18

• Most cases of trisomy 18 are traced to nondisjunction in meiosis II of the oocyte

• Oddly clenched fists, abnormally shaped and low-set ears, a small mouth and face.

Edward syndrome



6.2.2 Sex Chromosome Aneuploidy





Syndromes


Sex Chromosome Aneuploidy: Female



• By 1959, karyotyping confirmed the presence of only one X chromosome.

• At birth, a girl with XO syndrome looks normal, except for puffy hands and feet caused by impaired lymph flow.

• Some with XO syndrome have impaired hearing and frequent ear infections due to a small defect in the coiled part of the inner ear.

• They cannot hear certain frequencies of sound.

a. XO Syndrome- Turner



• At sexual maturity, thin body hair develops, but the girls do not ovulate or menstruate, and their breasts do not develop.

• The uterus is very small, but the vagina and cervix are normal size.

• In the ovaries, oocytes speed through development, depleting the supply during beginning of menstruation.




• Hormones (estrogen and progesterone) can be given to stimulate development of secondary sexual structures.

• Growth hormone can be prompt to maximize height.

• Individuals who are mosaics* may have children, but their offspring are at high risk of having abnormal numbers of chromosomes.

• Susceptible to osteoporosis, types 1 and 2 diabetes, and colon cancer.




• Having an extra X chromosome in each of her cells.

• The only symptoms are tall stature and menstrual irregularities.

• less intelligent than their siblings but rarely retarded.

b. Triplo-X



Sex Chromosome Aneuploidy: Male



• Severely affected men are underdeveloped sexually, with immature testes and prostate glands

• Having sparse pubic and facial hair and they are slow learners.

• They have very long arms and legs, large hands and feet, and may develop breast tissue.

• Testosterone injections during adolescence can limit limb lengthening and stimulate development of secondary sexual characteristics.

a. XXY Syndrome- Klinefelter



• A male with an extra X chromosome and an extra Y chromosome.

• Tend to develop foot and leg ulcers, resulting from poor venous circulation.

• Childhood and adolescence often include attention deficit disorder, obsessive compulsive disorder, and learning disabilities.

• In the teen years, testosterone level is low, development of secondary sexual characteristics is delayed, and the testes are undescended

b. XXYY Syndrome



• XXYY Syndrome and Klinefelter are hard to be distinguih.

• XXYY Syndrome share many characteristics Klinefelter , however XXYY Syndrome have more severe behavioral problems.

• Klinefelter can fathered children, with medical assistance where else man with XXYY syndrome is infertile.

Klinefelter vs XXYY Syndrome



• 96% of XYY males are apparently normal.

• Symptoms attributable to the extra chromosome may be great height, acne, and perhaps speech and reading problems.

• Prevalence of XYY are more psychological than biological.

c. XYY Syndrome- Jacobs syndrome



• Geneticists have never observed a sex chromosome constitution of one Y and no X.

• Y chromosome carries little genetic material.

• The absence of X chromosome which having more gene would not support the development of YO embryo beyond a few cell divisions.

Why no sex chromosome constituted of Y alone?



1. What happens during meiosis to produce the increased risk of trisomy 21 Down syndrome in the off spring of a woman over age 40 at the time of conception?

2. Describe an individual with each of the following chromosome constitutions. Mention the person’s sex and possible phenotype.

a. 47,XXX

b. 45,X

c. 47,XX, trisomy 21

3. How many chromosomes would a person have who has Klinefelter syndrome and also trisomy 21?



4. Explain why a female cannot have XXY syndrome and a male cannot have XO syndrome.

5. A couple has a son diagnosed with XXY syndrome. Explain how the son’s chromosome constitution could have arisen from either parent.

6. Distinguish among Down syndrome caused by aneuploidy and mosaicism.

7. Which chromosomal anomaly might you expect to find more frequently among the members of the National Basketball Association than in the general population? Cite a reason for your answer.



6.3 Abnormal ChromosomeStructure



• Structural chromosomal defects:

• Missing genetic material

• Extra genetic material

• Inverted genetic material

• Combined or exchanged parts of non-homologs (translocations)

Introduction




• Deletions (missing) and duplications (extra) DNA sequences.

• More genes involved, the more severe the associated syndrome.

• Small duplications do not affect the phenotype, but larger ones may.

• Often arise “ de novo, ” which means that neither parent has the abnormality, and it is therefore new.

a. Deletions and Duplications



a. Deletions and Duplications


Adopted from Human Genetics concepts and Application 9th ed.Chromosome 15

• Deletions and duplications can arise from chromosome rearrangements.• These include translocations, inversions, and ring chromosomes


a. Disorders of Deletions and Duplications


1. A young boy who had difficulty concentrating and sleeping and would often scream for no reason had a small duplication in chromosome 7.

2. A young girl plagued with head-banging behavior, digestive difficulties, severe constipation, and great sensitivity to sound had a microdeletion in chromosome 16.

3. Ashley Elizabeth Naylor had a cri-du chat (cat cry) syndrome aka 5p− syndrome where part of the p arm of one copy of chromosome 5 is missing; intellectual disability and developmental delay.


Translocation


Robertsonian translocation

Reciprocal translocation


b. Translocation Down Syndrome


• In a translocation, different (non-homologous) chromosomes exchange or combine parts.

• A translocation can affect the phenotype if it breaks a gene or leads to duplications or deletions in the chromosomes of offspring.

• In 1 in 20 cases of Down syndrome, a parent has a Robertsonian translocation between chromosome 21 and another, usually chromosome 14.


A case study in Robertsonian translocation


• The short arms of two different acrocentric chromosomes break.

• leaving sticky ends on the two long arms that join, forming a single, large chromosome with two long arms (chromosome 14/21).

• The tiny short arms are lost, but their DNA sequences are repeated elsewhere in the genome, so the loss does not cause symptoms; having 45 chromosomes.

• Even so, he or she may produce unbalanced gametes.


Translocation carrier


A Robertsonian translocation



b. Reciprocal translocation


• In a reciprocal translocation, two non-homologous chromosomes exchange parts.

• genes C, D, and E on the blue chromosome exchange positions with genes M and N on the red chromosome.



b. Reciprocal translocation


• If the chromosome exchange does not break any genes, the person is healthy and a translocation carrier.

• He or she has the normal amount of genetic material, but it is rearranged.

• FISH can be used to highlight the involved chromosomes

Adopted from Human Genetics concepts and Application 9th ed. The pink chromosome with the dab of

blue, and the blue chromosome with a small section of pink, are the translocated chromosomes

Fluorescence in situ hybridization


c. Inversions


• An inverted sequence of chromosome bands which disrupts important genes effects, in only 5 to 10 percent of cases.

• If neither parent has the inversion, then it may arose in a gamete

• Two types of inversions are distinguished by the position of the centromere relative to the inverted section:• Paracentric inversion• Pericentric inversion


i. Paracentric inversion


• Four different outcomes are to be seen if a crossover occurs with the normal homolog:• One normal chromatid (1)• One inverted chromatid (3)• One with two centromeres

(dicentric)(2)• One with no centromere (an

acentric fragment)(4)

• A paracentric inversion does not include the centromere in the loop. Adopted from Human Genetics concepts and

Application 9th ed.



i. Paracentric inversion


• In dicentric two centromeres are pulled to opposite sides of the cell, and the chromosome breaks, leaving pieces with extra or missing segments when the cell divides.

• In acentric fragment When the cell divides, the fragment is lost because a centromere is required for cell division



ii. Pericentric inversion


• A pericentric inversion includes the centromere within the loop.

• A crossover of homologous produces two chromosomes that have duplications and deletions, but one centromere each.


d. Isochromosomes and RingChromosomes


• A chromosome that has identical arms due to the centromeres part in the wrong plane.

• Isochromosomes are known for chromosomes 12 and 21 and for the long arms of the X and the Y.



d. Isochromosomes and RingChromosomes



• Ring chromosomes may arise when telomeres are lost, leaving sticky ends that adhere.

• Most ring chromosomes consist of DNA repeats and do not affect health, however some do.

• 6-year-old Cara Ford lost the ability to walk, talk, or eat and developed seizures in the event of ring chromosome 20


Summery of Chromosomal Aberrations




1. For an exercise in a college genetics laboratory course, a healthy student constructs a karyotype from a cell from the inside of her cheek. She finds only one chromosome 3 and one chromosome 21, plus two unusual chromosomes that do not seem to have matching partners.a. What type of chromosomal abnormality does she have?b. Why doesn’t she have any symptoms?

2. List three examples illustrating the idea that the amount of genetic material involved in a chromosomal aberration affects the severity of the associated phenotype.

3. Define or describe the following technologies:a. FISHb. Amniocentesis

ch6 chromosomal aberrations

Science

pearson education

extra chromosome

single chromosome

total chromosome

pratheep sandrasaigarandiagram

pratheep sandrasaigaranadopted

extra nonsex chromosome

abnormal chromosomes