Pedigree/numerical chrom

Question 1

The pedigree (or family history) is ______

Answer 1

a graphical representation of the family tree

Question 2

proband

Answer 2

The affected member through whom a family with a genetic disorder is brought to attention

Question 3

consultand

Answer 3

the person who brings the family to attention (can be affected or unaffected)

Question 4

consanguineous matings

Answer 4

Couples who have >1 known ancestors in common

Question 5

Phenotype:

Answer 5

the observable expression (of a genotype) as a morphological, clinical, cellular, or biochemical trait

Question 6

Genotype:

Answer 6

the set of
alleles that make up his or
her genetic constitution (usually we are talking about a single locus)

Question 7

Two types of structural abnormalities:

Answer 7

Balanced

unbalanced

Question 8

Balanced:

Answer 8

normal complement of chromosomal material

1. Inversions
2. Reciprocal translocations
3. Robertsonian translocations

Question 9

Unbalanced:

Answer 9

abnormal chromosomal content 1. Deletions

2. Duplications
3. Isochromosomes
4. Marker (ring) chromosomes!

Question 10

Structural Rearrangements Require

Answer 10

Double Strand Breaks of the DNA

Question 11

95% of patients with CML have _______

Answer 11

the Philadelphia chromosome and an abnormal chromosome 9

Question 12

Reciprocal Chromosome Translocation Leads to

Answer 12

to Chronic Myelogenous Leukemia

Question 13

Robertsonian translocations can give rise to _________

Answer 13

trimsomy 21

Question 14

Isochromosomes

Answer 14

refers to a chromosome in which one arm is missing and the other arm is duplicated in a mirror-like fashion

Question 15

two models for isochromosomes

Answer 15

1) mis-division through the CEN in meiosis II

2) exchange between one arm of a chromosome and its homolog at the proximal edge of the arm, adjacent to the centromere

Question 16

most common isochromosome is one involving the

Answer 16

long arm of the chrom

Question 17

_____& of the viable offspring of a carrier of isochromosome 21 are abnormal

Answer 17

100

Question 18

Summary of Mechanisms that Lead to Down Syndrome

Answer 18

•meiosis I nondisjunction (maternal) (95% of Down patients) e.g. 47,XY,+21
•Robertsonian translocation (4% of patients) e.g. 46,XX,der(14;21)+21
•Isochromosome (21q21q translocation) e.g. 46,XY,i(21)+21
•Mosaic Down syndrome
phenotype can be milder than typical trisomy 21, but patients exhibit wider variability in phenotypes due to variable portion of trisomy 21 cells in the embryo during development
•Partial trisomy 21
very rare, has only a portion of chromosome 21 duplicated!

Question 19

Aberrant Recombination Events Lead to

Answer 19

Unbalanced

Chromosomal Rearrangements

Question 20

Charcot-Marie-Tooth CMT 1A1

Answer 20

Charcot-Marie-Tooth CMT 1A1

– duplication of the gene for peripheral myelin protein-22, 17p11.2

Question 21

Hereditary neuropathy with liability to pressure palsies

Answer 21

– deletion of the gene encoding peripheral myelin protein-22, 17p11.2

Question 22

Hereditary sensory motor neuropathy - a genomic disorde

Answer 22

1. Charcot-Marie-Tooth CMT 1A1

2. Hereditary neuropathy with liability to pressure palsies

Question 23

Contiguous gene syndromes

Answer 23

1. Velocardiofacial syndrome
cleft palate and septal defects
2. diGeorge syndrome
neural crest, branchial pouches, great vessels
outflow tract defects in the heart

Question 24

Prior to the initiation of meiosis,

Answer 24

cells complete one round of DNA replication

Question 25

Meiosis is a

Answer 25

type of cell division in which diploid germ line cells give rise to haploid gametes.

Question 26

Two key differences between mitosis and meiosis are that

Answer 26

1. paternally- and maternally- derived homologous chromosomes pair at the onset of meiosis (prophase I), whereas the two homologs segregate independently in mitosis;
2. reciprocal recombination events between maternal and paternal sister chromatids generate chiasmata (physical linkages) between homologs.

Question 27

recombination between homologs is rare during ______

Answer 27

mitosis

Question 28

Meiotic prophase I is a critical period during meiosis.

Answer 28

Maternal and paternal homologs of each chromosome become paired or synapsed along their entire lengths, forming structures known as “bivalents”.
This process requires the formation of a proteinaceous structure called the synaptonemal complex. Reciprocal recombination events occurring at this stage generate physical links between homologs. These attachments, or crossovers, are also known as chiasmata.

Question 29

synaptonemal complex, promotes

Answer 29

inter-homolog interactions

Question 30

On average,________, resulting in geneticreassortment between chromosomes.

Answer 30

2-3 crossovers occur on each chromosome,

Question 31

Importantly, the synaptonemal complex disassembles at the end of ______ and bivalents are therefore held together only by ______

Answer 31

prophase 1

chiasmata

Question 32

______ is the most error-prone step of the process, and _______ at this stage is the most frequent mutational mechanism in humans.

Answer 32

Meiosis I

chromosome nondisjunction

Question 33

In the first meiotic division,

Answer 33

homologs are segregated to opposite poles of the cell.

Question 34

Unlike mitosis, chromosomes undergo a second round of segregation in ______. Meiosis II is very much like a_______

Answer 34

in meiosis II without an intervening round of DNA replication.

mitotic division.

Question 35

Genetic consequences of meiosis:

Answer 35

A. reduction in chromosome number from diploid to haploid
B. random segregation of homologous chromosomes, giving ~8x106 (or 223 ; 2
homologs for each of 23 chromosomes) different possibilities
C. random shuffling of genetic material due to crossover events, resulting in a vast
increase in genetic variability from the above estimate

Question 36

Mitosis

Answer 36

A. one round of chromosome segregation, resulting in daughter cells identical in
chromosomal content to the parental cell
B. DNA replication precedes each round of chromosome segregation
C. no pairing of homologous chromosomes
D. infrequent recombination
E. centromeres on paired sister chromatids segregate at each anaphase

Question 37

Meiosis

Answer 37

A. two rounds of chromosome segregation without an intervening round of DNA
replication
B. parental cells must be diploid and the chromosome number is halved in the
resultant cells
C. requires the pairing of homologous chromosomes and recombination for its
successful completion
D. centromeres on paired sister chromatids divide only at anaphase II in a normal
meiosis

Question 38

mitosis occurs in

Answer 38

occurs in somatic cells and in germ line precursor cells prior to entry into meiosis

Question 39

meiosis occurs in

Answer 39

germ line only

Question 40

Metacentric

Answer 40

the centromere is located in the middle of the chromosome such that the two chromosomes arms are approximately equal in length

Question 41

submetacentric

Answer 41

the centromere is slightly removed from the center

Question 42

acrocentric

Answer 42

the centromere is near one end of the chromosome

Question 43

Chromosomes are also classified cytogenetically based on

Answer 43

banding patterns observed microscopically after treatment with stains such as Giemsa, quinocrine, DAPI (4’,6- diamino-2-phenylindole), Hoechts, etc.

Question 44

chromosome patterns result from

Answer 44

These patterns result from the differential staining of various chromosomal regions (e.g. regions with high G+C, or A+T base compositions, or the presence of heterochromatin) with the dyes listed above. The banding pattern is unique to each human chromosome and allows the unequivocal identification of each chromosome.

Question 45

Somatic chromosomal errors that occur during development lead to

Answer 45

chromosomal mosaicism. Examples: 47,XX +21/46,XX (mosaic Down syndrome); 46, XX/46,XY (true hermaphroditism)

Question 46

Somatic chromosomal mutation is a common mechanism through which

Answer 46

cell lines come to overexpress oncogenes or lose tumor suppressor genes.

Question 47

Mosaic parents with mild phenotypes can have

Answer 47

fully affected offspring.

Question 48

X turner syndrome

Answer 48

Short stature, 
webbed neck, 
edema of hands and feet,
 broad shield-like chest, 
narrow hips, 
renal and cardiovascular anomalies, 
gonadal dysgenesis (failure of ovarian maintenance).

Question 49

XXY – Klinefelter syndrome

Answer 49

Tall stature,
hypogonadism,
elevated frequency of gynecomastia,
high frequency of sterility, language impairment

Question 50

Trisomy 13 – Patau syndrome

Answer 50

Characteristic facies, 
severe intellectual disabilities
Congenital malformations – holoprosencephaly, 
facial clefts, 
polydactyly, 
renal anomalies

Question 51

Trisomy 18 – Edwards syndrome

Answer 51

Intrauterine growth retardation, characteristic facies,
severe intellectual
disabilities,
characteristic hand positioning.
Congenital malformations – valvular heart disease,
posterior fossa
CNS maldevelopment, diaphragmatic hernias,
renal anomalies

Question 52

Trisomy 21 – Down syndrome

Answer 52

Characteristic facies,
short stature,
hypotonia,
moderate intellectual disabilities Congenital malformations – endocardial cushion defects, duodenal atresia and
other gastrointestinal anomalies, Hirschprung disease.

Question 53

maternal age two hit theory

Answer 53

The first “hit” is diminished recombination, caused either by a lack of chiasma or their mislocalization, resulting in a chromosome more susceptible to possible nondisjunction. The ability of oocytes to successfully complete chromosome segregation in the presence of unfavorable recombination events is thought to diminish over time, representing the second “hit” in this model.

Question 54

Aneuploidy is the

Answer 54

condition in which cells contain an abnormal chromosome number.

Question 55

nondisjunction,

Answer 55

the missegregation of chromosomes at metaphase in either mitosis or meiosis, such that daughter cells receive extra or fewer than the normal number of chromosomes.

Question 56

Monosomy

Answer 56

Monosomy describes the condition in which a cell lacks one copy of a chromosome,

Question 57

trisomy is the

Answer 57

situation in which an extra copy of an entire chromosome is present in the cell

Question 58

Mechanism of nondisjunction:

Answer 58

Meiotic recombination events (crossovers) are essential for tethering homologous chromosomes during the first meiotic division. Not surprisingly, disturbances in the recombination pathway are associated with abnormalities in chromosome segregation in the first meiotic division.

Question 59

Nondisjunction events are related to the positioning

Answer 59

chiasmata; crossover events that occur too near or too far from the centromere increase chromosome nondisjunction. Centromere-distal exchanges are less effective in ensuring appropriate spindle attachment and separation of paired homologs in meiosis centromere-proximal or excessive numbers of exchanges lead to entanglement of paired homologs in MI that then undergo reductional division leading to what appears to be MII errors.

Question 60

Nondisjunction events are also related to the frequency of

Answer 60

the frequency of crossover events. The reduction or absence of recombination events increases the likelihood of nondisjunction.

Question 61

metracentric

Answer 61

centromere in middle of chrome

Question 62

submetacentric

Answer 62

centromere slight removed from center

Question 63

acrocentric

Answer 63

centromere near 1 end

Question 64

mosacism is

Answer 64

presence of 2 genetically different cells in tissue from 1 zygote