CYTOGENETICS 1

Question 1

WHAT DO CHROMOSOMAL ABNORMALITIES OCCUR IN?

Answer 1

– perinatal deaths, mentally retarded, patients with inborn defects, infertile couples (repeated
spontaneous abortions, sterility) and infertile men

Question 2

HOW BIG IS THE PROPORTION OF ABORTIONS CAUSED BY CHROMOSOMAL ABNORMALITIES?

Answer 2

-> 30% spontaneous
-> 50% of early abortions between 8-15 weeks, most of the zygotes are lost before recognition of pregnancy - results in strong menstruation

Question 3

WHAT PERCENTAGE OF LIVE BORN BABIES HAVE CHROMOSOMAL ABNORMALTIES?

Answer 3

0.6%

Question 4

WHAT ARE THE CONGENITAL NUMERICAL CHROMOSOMAL ABNORMALITIES?

Answer 4

aneuploidy
polyploidy

Question 5

WHAT ARE THE STRUCTURAL CHROMOSOMAL ABNORMALITIES?

Answer 5

balanced
unbalanced

-> difference between them both is that in unbalanced there are genes missing or genes added, while in balanced there is no addition of missing genes - they are just rearranged

Question 6

DEFINE ANEUPLOIDY

Answer 6

one chromosome missing or in addition
-trisomy 2n+1
-monosomy 2n-1

Question 7

DEFINE POLYPLOIDY

Answer 7

multiplication of haploid set
-> lethal – abortion, if children are born, they will die soon after birth,
-triploidy 3n
-tetraploidy 4n

Question 8

NAME THE 3 TYPE OF BALANCED CHROMOSOMAL ABNORMALITIES

Answer 8

-Inversion / insertion
-Reciprocal translocation
-Robertsonian translocation

Question 9

NAME THE 5 TYPE OF UNBALANCED CHROMOSOMAL ABNORMALITIES

Answer 9

-Deletion
-Duplication
-Ring chromosome
-Dicentric chromosome
-Isochromosome

Question 10

HOW ARE ACCQUIRED CHROMOSOMAL ABNORMALITIES FORMED?

Answer 10

via mutagens (clastogenes) and time
-> not all genes form mutations
-> chromatid and chromosome breaks, chromatid exchanges, chromosome exchanges, rings, translocations, dicetrics

Question 11

DEFINE MOSAIC

Answer 11

• 2 or more cell lines with different karyotypes
• origin from one cell during mitotic division of zygote

Question 12

DEFINE CHIMAERA

Answer 12

• formed by the fusion of 2 zygotes
• fertilization of egg and polar body each by sperm with different gonosome
  -karyotype 46,XX/46,XY
  -origin from 2 cell lines / zygotes
  -very rare

Question 13

DISCUSS DISPERMY

Answer 13

-possible way of triploidy
-most common way of triploidy
-lethal
-egg + 2 sperm
-23 + 23 + 23 = 69 chromosomes
-additional set of chromosomes from father -> partial mole

Question 14

DIPLOID OVUM + HAPLOID SPERM

Answer 14

• possible way of triploidy
• 46+23 = 69 chromosomes
• nonmolar product
• lethal

Question 15

DISCUSS HAPLOID OVUM AND DIPLOID SPERM

Answer 15

• possible way of triploidy
• 23+46 = 69 chromosomes
• additional set of chromosomes from father -> partial mole
• lethal

Question 16

WHAT IS A COMPLETE MOLE?

Answer 16

• formed by the fertilization of an enucleated (no nucleus) egg, only paternal genome (duplicates → 46 chromosomes)
• A hydatiform complete mole is caused by a single sperm (90% of the time) or two (10% of the time) sperm combining with an egg which has lost its DNA. In the first case, the sperm then reduplicates, forming a “complete” 46 chromosome set

Question 17

EXPLAIN TETRAPLOIDY

Answer 17

• formed by endoreduplication → division of chromosomes without division of cell (in mitosis)
• 92 chromosomes
• formed post-zygotically

Question 18

GIVE AN EXAMPLE OF PARTHENOGENESIS IN HUMANS

Answer 18

OVARIAN TERATOMA
- duplication of chromosome and division of unfertilized ovum (diploid)
- benign tumor which my have teeth and hair
- only maternal genome

Question 19

EXPLAIN NONDISJUNCTION IN MEIOSIS

Answer 19

-M1: undivided homologous chromosomes → disomic gametes
-M2: undivided sister chromatids → nullisomic gamete

→ fertilization → monosomy/trisomy

Question 20

EXPLAIN NONDISJUNCTION IN MITOSIS

Answer 20

undivided chromatid into daughter cell resulting in a mosaic

Question 21

WHAT ARE THE CAUSES OF NONDISJUNCTION?

Answer 21

nondisjunction of 21 occurs 4x more often in oogenesis than spermatogenesis and at the same time 4x more often in M1 than M2
- internal causes – individual risk of individual chromosomes to nondisjunction; increases with age of women above 35 and men above 50
- in women above 35 – error in M1 – aging of egg, dysfunction of mitotic spindle, changes in intracellular environment (due to decrease of hormonal function) and accumulation of mutagens during women’s life
- error in M2 – delayed fertilization due to over matured egg
- external causes – external mutagens - not main factors of nondisjunction

Question 22

EXPLAIN THE ORIGIN OF MOSAICS FROM TRISOMIC GAMETES

Answer 22

• loss of chromosome from trisomic gamete by anaphase lag
• monosomy can form → if healthy cell loses a chromosome, there are 45 left

Question 23

NAME AND EXPLAIN 3 CONSEQUENCES OF CHROMOSOMAL ABNORMALITIES

Answer 23

MONOSOMY X = only monosomy is compatible with life, but 99% of X monosomies are aborted

AUTOSOMAL MONOSOMY = always lethal and aborted

AUTOSOMAL TRISOMY = some have a chance to be born (trisomies 21, 18, 13, mosaic 8)
-abortions also seen (trisomy 16)

Question 24

DOWN SYNDROME (TRISOMY 21)

Answer 24

-47 chromosomes
frequency of live births - 1/800 (but 75% foetuses are aborted)
- 95% cases with DS are free trisomies, 5% are translocation trisomies, which are formed by Robertsonian translocation
(fusion of long arms of both acrocentric chromosomes which then divide as one chromosome)
-carrier of Robertsonian translocation has no clinical symptoms
- 1% of patients with DS have a mosaic
- risk for child increases with the age of mother – 35yrs = 1/350, 40yrs = 1/100, 45y.o= 1/25
-> pregnancy of mother above 35 y.o. is an automatic risk = prenatal screening
-> for translocation form of DS, the age does not matter and they have 46 chromosomes
- phenotype of DS - face – abnormal slant of palpebral fissures, round face, flat nasal bridge, big tongue (does not fit in the mouth, that is why the mouth is constantly semi open)
o short fingers, short stature, mental retardation
o in free trisomy and translocation form the phenotype is the same
o often tumours (especially leukaemia) – trisomy cells are more prone to mutagens

Question 25

EDWARDS SYNDROME (TRISOMY 18)

Answer 25

do not live long, max. few months – 18. -Chromosome has a lot of genes that are necessary for survival - frequency of live births - 1/5000 - symptoms – prolonged occipital part of skull, dysmorphic features of face, low set malformed ears, short sternum, abnormal overlapping fingers, severe malformations of heart or other organs, severe retardation of development

Question 26

PATAU SYNDROME (TRISOMY 13)

Answer 26

karyotype 47XX + 13 or 47XY + 13 - frequency of live births - 1/10 000 - 20% translocation form 13/13 or 13/14 - Clinical symptoms – dysmorphic features of face, microcephaly, polydactyly, cleft lip and palate, severe organ malformation (heart defect, CNS), severe retardation of development - Death after a few weeks post birth - lots aborted before this

Question 27

TURNER SYNDROME (MONOSOMY X)

Answer 27

-45,X or mosaics -1/5000 liveborn girls (but 99% fetuses are aborted) -does not depend on age of mother -patient with TS –> syndrome formed by postzygotic loss of X chromosome -aborted fetuses –> formed by the fertilization of nullisomic gamete -severe circulation complications -if a mother has a daughter with TS, there is no increased risk for the next child -in the case of 45, X there is a loss of paternal chromosome in 77% cases (delay of chromosome) -karyotype with 46, X,i(Xq) is fertile – missing short arm of one chromosome, second X chromosome is normal -> development of gonads is critically conditioned to the region on long arm q- in the loss of p arm there is no loss of genes which are involved in gonad development -> fertility is not affected - karyotype with 46, X,i(Xp) has gonad dysgenesis - karyotype with Y chromosome has a risk of malignant gonads -Clinical symptoms - small stature, sterility, underdeveloped secondary sexual characteristics, amenorrhea, neck webbing, low hair line, mostly normal intelligence, in new-borns oedema on foot

Question 28

KLINEFELTER SYNDROME

Answer 28

-most common karyotype of 47,XXY -need at least 1Y and more than 1X -47,XXY / 48,XXYY or 48,XXYY / 49,XXXXY / 46,XY/47,XXY -frequency of live births in boys - 1/1000 - not only 47, XXY, but anything that has at least 1Y and at the same time more than 1X (so XXXY, XXYY, XXXXY etc.) - in 1/3 cases it is due to the nondisjunction in M1 of father, 47% nondisjunction in M1 of mother (age dependent), 22% nondisjunction in M2 of mother - the more X, the taller the stature and lower the IQ - Clinical symptoms - sterility (azoospermia = no sperm in ejaculate), hypogonadism (atrophy of testes), secondary sexual characteristics of women (eunuchoid appearance) - „Klinefelter is born as the last child in the family. “– a saying, because the risk of the syndrome increases with mothers age

Question 29

TRIPLE X SYNDROME

Answer 29

-47,XXX -1/1000 women affected -normal phenotype, fertile, risk of schizophrenia

Question 30

SYNDROME 2 Y

Answer 30

-47,XYY -1/1000 men affected -normal phenotype, tall, chance of increased aggression

Question 31

DO MEN CONTRIBUTE TO AN INCREASED RISK IN CHROMOSOMAL ABNORMALITIES?

Answer 31

yes if over the age of 50

Question 32

DOES AN INCREASE IN THE MOTHERS AGE INCREASE THE RISK OF LOSS OF CHROMOSOME IN ANAPHASE?

Answer 32

no it does not

Question 33

WHAT IS THE KARYOTYPE OF CHIMERAE?

Answer 33

46,XX/46,XY

Question 34

WHAT IS THE KARYOTYPE OF OVARIAN TERATOMA IN WOMEN?

Answer 34

46,XX

Question 35

WHAT ARE NOT COMPATIBLE WITH LIFE?

Answer 35

autosomal monosomies

Question 36

DOES AN INCREASE IN THE MOTHERS AGE INCREASE THE RISK OF ALL CHROMOSOMAL ABNORMALITIES?

Answer 36

no

Question 37

WHAT DOES A COMPLETE HYDRATIFORM MOLE CONTAIN?

Answer 37

paternal genome only

Question 38

WHAT IS THE PARTIAL MOLE DUE TO?

Answer 38

triploidy with an additional set of paternal chromosomes

Question 39

DOES AN INCREASE IN THE MOTHERS AGE INCREASE THE RISK OF NONDISJUNCTION?

Answer 39

yes