Exam 1: Lecture 12

Question 1

purpose of medical cytogenetics

Answer 1

part of clinical medicine that studies a relationship between chromosomal alterations and genetic disease in humans (new and clinical aspect)

Question 2

why do clinicians need to know about chromosomes

Answer 2

screening for chromosomal abnormalities (miscarry) disorders (infertility and miscarriages), and anomalies. aslo screening (imbalances) and cancer cell acquire chrom abnormalities

Question 3

constitutional abnormalities (homogenous)

Answer 3

before a birth; acquired in oocyte or spermatozoon. every cell in zygote will be affected (homogenous)

Question 4

constitutional abnormalities (mosaic)

Answer 4

anomaly may originate in zygotic divisions, not all cells are equally affected (mosaic state)

Question 5

acquired abnormalities

Answer 5

chromosome anomaly in fully differentiated or undifferentiated cells, leads to cancer cells (ex blood skin)

Question 6

reasons for cytogenetic testing: prenatal analysis

Answer 6

specimen type: amniotic fluid/chorionic villi

-family history, older women, abnormal ultrasound

Question 7

reasons for cytogenetic testing: postnatal analysis

Answer 7

major specimen is peripheral blood

-family history, multiple miscarriages, birth defects, delays, abnormal growth/develop

Question 8

reasons for cytogenetic testing: cancer

Answer 8

specimen type: bone marrow/peripheral blood/lymph node/tumor

-hematological malignancies ( leukemia/lymphoma), solid tumors (-blastoma/-sarcoma)

Question 9

general steps of diagnostic teesting workflow

Answer 9

pt -> specimen sample -> chromosome, FISH or microarray -> results

Question 10

g banding pros

Answer 10

rapid and robust, detect numerical abnormalities; structural chromosomal rearrangements; large deletions/duplications

Question 11

g banding cons

Answer 11

require a lot of training, 5-10 Mb, low-level or tissue specific mosaicism missed, no epigenetics, can’t detect cancer

Question 12

FISH pros

Answer 12

does not require dividing cells (directly analyze blood, tumor, amniotic fluid), no culture need to be established (multiple tissues application), detect translocations important in cancer; probes are dual color, large number of cells for mosaicism

Question 13

FISH cons

Answer 13

need to know what the pt has bc probe dna is complementary to known segment of dna, costly, no epigenetic changes detected

Question 14

what is dna microarray

Answer 14

molecular-cytogenetic method for analysis of copy number variations (CNVs) copy number variation -> gains or losses of genomic material

Question 15

microarray pros

Answer 15

detects deletions/duplications/amplifications, detect an imbalance at 5kb or more, physician does not need to know what pt has, easy to assess recessive genes/haploinsufficient genes, small amt dna even from solid tumors

Question 16

microarray cons

Answer 16

cannot detect balanced translocations, imbalances not known are not detected, sensitivity for low-level mosciasm is reduced by constitutional samples or tumor heterogeneity, interpreting CNVs

Question 17

why, in dna microarray, does the con: challenge in interpretation of dna CNVs, turn into a pro about the field of genetics

Answer 17

about 20,000 genes and we know roughly 6,000; if we detect dup of deletion of a gene we do not know, “variant of unknown significance”. the field is developing and new discoveries of genes/phenotypes happen everyday. we even collab w/ entire world to learn about new genes!

Question 18

why does it take 6 mo to 1 yr to launch clinical use of microarray

Answer 18

extensive validation of a chosen platform

need to learn probe behavior, artifacts, how dups and deles are detected, many samples needed to understand probes and how platform does with sensitivity

Question 19

reciprocal translocations detected w/ microarray?

Answer 19

no