Biochem Exam 3: Chromosomal Abnormalities

Front 1

2 major genetic materials in humans:

Back 1

1 nuclear chromosomes (46 chromosomes)
2. mitochondrial chromosomes (circular, 37 genes)

Front 2

Chromosomal make-up of humans

Back 2

*22 pairs of autosomes
*2 sex chromosomes (XX, XY)

46, XY = designation (total # and sex)

Front 3

chromosomal differences btwn somatic and reproductive cells

Back 3

somactic cells have 46 chromosomes (diploid)

oocytes/sperm cells (=gametes) have 23 nuclear chromosomes (haploid)

Front 4

How are chromosomes are replicated during mitosis

Back 4

-DNA synthesized during S phase
-Sister chromatids form
-Disjunction of sister chromatids during mitosis (M phase)

Front 5

How are chromosome segregated during meiosis I and meiosis II?

Back 5

meiosis I: meiotic crossover (genetic recombination) occurs--> increasing genetic diversity in the gamete, disjunction of chromosomes occurs

meisosis II: disjunction of sister chromatids, chromosome number is reduced in half (back to original #)

Front 6

What are the consequences of non-disjunction during mitosis and meiosis

Back 6

-Non-disjuction during MITOSIS results in one daughter cell ending up with an extra chromsome and one missing a chromosome = mosaicism= cell populations w/ diff genetic make-up (frequently occurs in cancer cells)
-Non-disjunction during MEIOSIS generates gametes w/ incorrect chromosome number, offspring will inherit abnormal chromosome, which can lead to spontaneous abortion or serious disease

Front 7

List basic types of karyotype deficiencies that lead to chromosomal abnormalities

Back 7

-abnormal chromsome number
-structural abnormalities
balanced (unequal crossover)
unbalanced (deletions or insertions)

Front 8

Down syndrome

Back 8

symptoms: short stature, short neck, flat nasal bridge, open mouth w/ protruding tongue, congenital heart disease, low IQ
karyotypes: 47, XX or XY, +21 (trisomy 21)
(+=extra)
*most common disease

Front 9

Trisomy 13 (Patau):

Back 9

symptoms: mental retardation, failure to thrive, congenital heart problems, sloping forehead, cleft-lip (& palate), polydactyl (>5 fingers or toes), fist clenching, rocker bottom feet
karyotypes: 47, XX or XY, +13

Front 10

Trisomy 18 (Edwards):

Back 10

symptoms:mental retardation, failure to thrive, congenital heart problems, receding jaw, low-set malformed ear, clenched fist, rocker bottom feet
karyotypes: 47, XX or XY, +18

Front 11

Cri du Chat:
(Autosomal deletion syndrome)

Back 11

symptoms: cat-like cry, mental & growth retardation, speech impairment, heart problems, small head, narrow eyes far apart, low-set ears
karyotypes: 46, XX or XY, del(5p)
(caused by deletions in the p arm of chromosome 5)

Front 12

Different genetic causes of Down syndrome

Back 12

1. mosaicism during early development (caused by non-disjunction during mitosis)--> 47, XX, +21 (95%)

2. Robertsonian translocation in a parent, translocation most commonly btwn 14 & 21--> 46, XX, rob(14;21),+21 (4%)

3. 21q21q translocation, long arms of two chromosome 21s join together

4. partial trisomy 21, only part of chromosome 21 is present in triplicate

Front 13

What is the Y chromosome gene that is the main regulator of male sexual development?

Back 13

SRY gene= TDF (testis-determining factor)
*default sex is female, SRY leads to male sex development

Front 14

Explain how chromosomal abnormalities in the SRY gene can lead to abnormal sexual development

Back 14

XX males-
incorrect crossover of SRY gene to the X chromosome, sterile (hypogonadism, azoospermia (no sperm in semen)
XY females-
loss of active SRY gene from the Y chromosome due to incorrect cross-over, deletion or mutation, sterile (streak gonad, no functional ovaries), secondary sex characteristics do not develop (no puberty)

Front 15

Explain the basic mechanism of X chromosome inactivation

Back 15

Silence genes on one X chromosome to ensure similar X gene dosage btwn males and females.
-inactivation directed by X inactivation center (XIC) located on q arm of X chromosome
-XIC produces large non-coding RNA (XIST) that initiates changes in histone composition & DNA methylation causing inactivation
-random
-occurs during early embryogenesis
-daughter cells in mitosis inherit the Xi pattern
-females are mosaic for X-linked gene expression

Front 16

Inactivated genes on Xi are not 100% silenced!! Where are most unsilenced genes located?

Back 16

-distal end of p arm (pseudoautosomal region)

*both X chromosomes necessary for female sex develpment! Females are mosaic for X-linked gene expression

Front 17

What is uniparental disomy and what can it lead to?

Back 17

when both chromosomes are inherited from the same parent
can lead to disorders involving genes under genomic imprinting

Front 18

What do most chromosomal abnormalities cause?

Back 18

mental retardation and developmental problems

Front 19

most frequent abnormal chromosome numbers (4)

Back 19

Euploid (total # multiple of 23)
1. triploid- 69 = death
2. tetraploid- 92 = death
Aneuploid (total # not multiple of 23)
3. trisomy- extra chromosome (common @ 21,18,13)
4. monosomy- missing chromosome (45X, Turner)

Front 20

Transcription factors SOX9 & DAX1, can also lead to XX males and XY females, each favor which sex?

Back 20

SOX9- favors male (XX), loss of function mutation
DAX1- favors female (XY), gene duplication

Front 21

Klienfelter syndrome

(sex chromosome abnormality)

Back 21

symptoms: tall, feminine like stature, hypogonadism (infertile), some learning deficiencies
karyotype: 47, XXY

Front 22

Turner syndrome

(sex chromosome abnormality)

Back 22

symptoms: short stature, streak gonads, can't enter puberty, infertile, some learning difficulties, webbed neck, edema, wide chest (man-like)
karyotype: 45, X

*46, XX mosaic is another karyotype for Turner that can be fertile

Front 23

Isochromosomes (i(Xq)), contain 2 long arms (q) of the X chromosomes, how are they formed?

Back 23

Isochromosomes form by incorrect separation of sister chromatids during meiosis II.

Front 24

Do mitochondrial or nuclear chromosomes have more chromosomes per cell?

Back 24

mitochondrial

Front 25

Do mitochondrial or nuclear chromosomes contain more genes?

Back 25

nuclear

Front 26

The Yp psuedoautosomal region on the Y chromosome contains what gene?

This region is present in _____ males and deleted in ____females

Back 26

SRY

present in XX males and deleted in XY females

Front 27

When the region of the Y chromosome containing AZFa, AZFb, and AZFc is deleted, what is the result?

Back 27

semen does not contain sperm

(azoospermia)