Human Genetics Biology 311
Fall 2004
Lecture 3: Chromosome Defects
Reading: Chap. 2 pp. 47-53
Outline:
1. Variation in number
2. Structural abnormalities
3. Meiosis of carriers
Lecture:
Chromosome abnormalities=changes that usually visibly alter the
chromosomes.
 caused by misrepair of broken chromosomes, improper recombination, or
improper segregation of chromosomes during mitosis or meiosis
Chromosome abnormalities can affect
 Germ cell (constitutional)
 Somatic cell
1. Variation in chromosome number
polyploidy: extra sets of chromosomes
 1-3% of human pregnancies
 very few survive to birth
 lethal; usually caused by 2 sperm fertilizing one egg
aneuploidy: one extra or one missing chromosome
trisomy: three copies of one chromosome
i.e. Down syndrome
47, XX + 21 or 47, XY + 21
have extra chromosome 21
monosomy: lack of a chromosome
i.e. Turner syndrome
45, X
monosomy for the X chromosome
mixoploidy: different numbers of chromosomes in different cells
mosaicism: An individual with a somatic chromosome defect will have a chimera
with different chromosome make-up in different cells.
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chimera: (more rare) Genetically different cell lineages in one individual
originating from different zygotes.
Examples/nomenclature of chromosome abnormalities: Box 2.4
Numerical Abnormalities
Triploidy
69, XXX; 69 XXY; 69 XYY (all lethal)
Trisomy
47, XX +21 (Down syndrome)
Monosomy 45, X (Turner syndrome)
Mosaicism 47, XXX/46, XX
Clinical consequences of numerical abnormalities:
 Serious, usually lethal
 Usually pleiotrophic effects=Multiple abnormalities in phenotype
 Imbalance in levels of gene products produced
 Wrong number of sex chromosomes has fewer deleterious effects than
wrong number of autosomes
 Autosomal monosomy invariably lethal in early embryo
 Trisomies less harmful than autosomal monosomies
 Trisomies 13, 18 and 21 can survive until birth
 Trisomy 21 may survive to age 40 or longer
2. Structural chromosome abnormalities
Chromosome breaks caused by
 Radiation damage
 Chemical damage
 Recombination
Breaks usually repaired by cellular enzymes
Structural abnormalities
 Breaks repaired incorrectly
 Give rise to other abnormalities when cells divide in mitosis or meiosis
 Balanced, no net gain or loss of chromosomal material; generally no effect
on phenotype
 Unbalanced: net gain or loss of chromosomal material; often get effect on
phenotype
Examples of structural abnormalities
Chromosome defect
Deletion*
Inversion
Duplication
Karyotype nomenclature
46, XY del (4) (p16.3) terminal deletion
46, XY inv (11) (p11p15)
46, XX dup (1) (q22q25) insertion into Chr.
2 a segment of Chr. 2
2
Insertion
Ring
Marker extra unidentified chromosome
Translocation, reciprocal
Translocation, Robertsonian (nonreciprocal)
46, XX ins (2) (p13q21q31)
46, XYr (7) (p22q36)
47, XX + mar
46, XX t (2;6) (q35;p21.3) balanced
45, XX der (14;21) (q10;q10)
translocation Down syndrome
*Nomenclature example:
#
chromosomes
46
Sex
chromosomes
XY
Abnormality
del
Chromosome
affected
(4)
Region
affected
(p16.3)
3. Meiosis of carriers
Carriers of structural abnormalities have a high risk of passing on these or other
abnormalities to the gametes due to abnormal segregation of the chromosomes
in meiosis or due to the nature of the products of crossing over events.
Example 1: Meiosis in a carrier of a balanced reciprocal translocation, Fig. 2.22
Zygotes produced from fertilization of the four types of gametes produced from
the carrier include
 Normal
 Balanced carrier
 Partial trisomy and partial monosomy (usually lethal)
 Partial monosomy and partial trisomy (usually lethal)
 Thus at least half the zygotes produced would not be viable
Example 2: Crossover events occurring in meiosis in heterozygotes for
paracentric inversions can result in production of dicentric and acentric
chromosomes which segregate in an unstable manner.
Example 3: Heterozygotes for pericentric inversions can have recombination
events that lead to formation of duplications and deletions.
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