Autosomes (definition, # & size)

non sex chromosomes

22 pairs

1-22, largest to smallest

Trisomy

3 copies of a chromosome

75% of chromosomes can't exist in trisomy and be compatible with life

Down syndrome

trisomy 21

caused by nondisjunction in mei I or II, or chrom 14/21 translocation

monosomy

only 1 copy of a chrom

usually incompatible with life

Klinefelter's

XXY

endocrine problems, tall stature, sterility

XYY

"aggression"

XXX

triple x syndrome

mild problems, growth issues

XO

Turner's syndrome

many die in utero, survivors--short stature, webbed neck, learning disabilities

microdeletion

chromosomal deletion spanning several genes that is too small to be detected under the microscope using conventional cytogenetic methods

contiguous gene syndrome

microdeletion that spans 2 or more genes tandemly positioned along a chrom

balanced vs unbalanced translocation

balanced=may or may not cause defect

unbalanced=results in extra or missing genes

Cytogenetic analysis

aka karyotyping

detects: monosomy, trisomy, big deletions, duplications, rearrangements

FISH

fluorescent in situ hybridization

detects microdeletions and duplications, but need to know what you're looking for so you can label it with a color

subtelomeric FISH

microdeletions and subtle rearrangements in the regions near the end of chromosomes (subtelomeric)

Microarray is first tier test for:

DD/ID/ASD, mult congenital anomalies, microcephaly, infantile spasms, tic disorders,

microarray results:

CNV (copy number variant)

duplications: strong signal

deletions: negative signal

+more diagnoses

-results are not always clear bc CNVs exist in general population

Pathogenic CNVs

>500kB

deletions or amplifications

contain genes expressed in CNS

may contain genes known to be mutated in CNS disorders

Benign CNVs

smaller

gene-poor

present in healthy relative

duplications>deletions

Risk CNVs

inherited

variable penetrance but occur more often in disease state

deletions or duplications

contain genes of CNS/known risk genes of CNS

Proband

person with disease

Gain of function diseases

often degenerative diseases

ex: toxicity function-->disease progression

X-linked diseases in males and females

males: hemizygous, full manifestation

females: doesn't behave as strictly as straight-up dominant/recessive disorders