Exam 1: Lecture 12 Flashcards
purpose of medical cytogenetics
part of clinical medicine that studies a relationship between chromosomal alterations and genetic disease in humans (new and clinical aspect)
why do clinicians need to know about chromosomes
screening for chromosomal abnormalities (miscarry) disorders (infertility and miscarriages), and anomalies. aslo screening (imbalances) and cancer cell acquire chrom abnormalities
constitutional abnormalities (homogenous)
before a birth; acquired in oocyte or spermatozoon. every cell in zygote will be affected (homogenous)
constitutional abnormalities (mosaic)
anomaly may originate in zygotic divisions, not all cells are equally affected (mosaic state)
acquired abnormalities
chromosome anomaly in fully differentiated or undifferentiated cells, leads to cancer cells (ex blood skin)
reasons for cytogenetic testing: prenatal analysis
specimen type: amniotic fluid/chorionic villi
-family history, older women, abnormal ultrasound
reasons for cytogenetic testing: postnatal analysis
major specimen is peripheral blood
-family history, multiple miscarriages, birth defects, delays, abnormal growth/develop
reasons for cytogenetic testing: cancer
specimen type: bone marrow/peripheral blood/lymph node/tumor
-hematological malignancies ( leukemia/lymphoma), solid tumors (-blastoma/-sarcoma)
general steps of diagnostic teesting workflow
pt -> specimen sample -> chromosome, FISH or microarray -> results
g banding pros
rapid and robust, detect numerical abnormalities; structural chromosomal rearrangements; large deletions/duplications
g banding cons
require a lot of training, 5-10 Mb, low-level or tissue specific mosaicism missed, no epigenetics, can’t detect cancer
FISH pros
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
FISH cons
need to know what the pt has bc probe dna is complementary to known segment of dna, costly, no epigenetic changes detected
what is dna microarray
molecular-cytogenetic method for analysis of copy number variations (CNVs) copy number variation -> gains or losses of genomic material
microarray pros
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
microarray cons
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
why, in dna microarray, does the con: challenge in interpretation of dna CNVs, turn into a pro about the field of genetics
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!
why does it take 6 mo to 1 yr to launch clinical use of microarray
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
reciprocal translocations detected w/ microarray?
no
