congenital and genetic disorders Flashcards
what are congenital abnormalities?
-BIRTH defects —>
result from PROBS in DEVELOPMENT in EMBRYO
(any non-genetic defect at birth!)
what is period of vulnerability?
-time in GESTATION where embryo is MOST sensitive to development ERRORS
time period of vulnerability is?
busy and sensitive; organogenesis (organs begin to form)
-15 to 60 days approx post conception
critical period is?
the time period for each organ system during development where they are particularly sensitive and any interruption in process may result in baby being born with congenital abnormality
CNS critical period?
2-4.5 weeks
CVS critical period?
2.5-5.5 weeks
limbs critical period?
3.5-7weeks
eyes critical period?
3.5-7.5 weeks
external genitalia period?
6.5 to 10 weeks
what is a teratogen?
any environmental factor causing congenital abnormality
-includes maternal environment AND environment surrounding mother
examples of teratogens?
example: radiation (affects cell function)
example: drugs/ chemicals (can cross placenta)- alcohol, thalidomide effect
example: microbes (pathogens/toxins)- screened early in pregnancy like rubella virus
example: cig smoke
are congenital abnormalities always due to a teratogen?
no, can be a result of a lack of something (like malnutrition)
what are the 4 genetic abnormalities
- monogenic
- polygenic/complex trait (multifactoral)
- mitochondrial gene disorders
- chromosomal defects
what is a monogenic abnormality?
- SINGLE gene
- caused by defective or mutant allele
- primarily affect CHILDREN
- pattern of inheritance depend on whether phenotype is DOMINANT or RECESSIVE and whether AUTOSOMAL or SEX chr
- –> leads to formation of ABNORMAL protein, or decreased protein production of gene product
- –> results in: defective enzyme or decreased amts of enzyme, defects in receptor proteins, alterations in non-enzyme proteins, mutations resulting in unsual rxns to drugs
3 types of monogenic abnormalities?
a) autosomal dominant
b) autosomal recessive
c) x-linked disorders or “sex linked”
what is autosomal dominant disorder?
- SINGLE mutant allele form affected parent transmitted to offspring regardless of sex
- autosomal= non-sex
- dominant= if defective allele is transmitted to offspring it will cause an abnormality
- affected parent has 50% chance of transmitting it
what is autosomal recessive disorder?
- BOTH alleles affected
- both parents could be unaffected but carriers
- affects sexes equally
- if one parent fully affected, all children carriers
- if both parents carriers: 25% child affected, 25% unaffected, 50% carriers
X-linked disorders or “sex linked”?
- most sex chromosome defects are on X (female) chromosome)—> males most affected because females are homogametic and have 2 X, male have one (heterogametic)
- unaffected mother carries 1 normal one mutant: 50% chance to sons, 50% chance daughters carrying
- affected father: transmits defective to daughters, does not transmit to son
polygenic/complex trait (multifactoral inheritance disorder)?
- caused by multiple genes (2 or more) and in many cases environmental factors (like viral infection)
- expressed during FETAL life and present at birth, or may be expressed LATER in life
- environmental factors play greater role in disorders that develop LATER
- multifactoral= someone could have predisposition but not get it b/c of good lifestyle
mitochondrial gene disorders?
- DNA not only in nucleus, some in MITOCHONDRIA
- 37 mitochondrial genes
- involved in production of ATP
- code for enzymes involved in electron transport chain (resp chain) in mitochondria
- only transmitted by MOTHER (maternal inheritance)
- b/c sperm tail falls off with mitochondrial genes in it
- most MITOCHONDRIAL defects show in NEUROMUSCULAR defects
- –> neurons and muscle cells have high requirement for OXIDATIVE metabolism (more ATP!)
chromosomal defects?
46 chromosomes, 23 pairs
-defect in NUMBER or STRUCTURE of chromosomes
what is a karytotype?
-TEST to identify and evaluate size, shape, number of chromosomes in sample of body cells
aneuploidy=
problem related to NUMBER of chromosomes
what is a numerical abnormality (chromosomal)?
aneuploidy, problem related to number of chromosomes (more or less than normal)
monosomy= one chromosome pair is LACKING
trisomy= EXTRA chromosome (downsyndrome is trisomy 21)
turners syndrome?
-female has missing sex chromosome
-1 in 2500 births, gametes XO not XY
can live with turners
klinefelters syndrome?
-male has extra X chromosome
XXY, 47 chromosomes
what is a structural defect (chromosomal)?
- under certain circumstances SECTION of CHROMOSOME can break OFF, detached segment can do 1 of 3 things:
1. deletion
2. inversion
3. translocation
what is deletion (structural)
LOST a piece of chromosome (one in pair)
- detached segment does NOT reattach
- LOSS of genetic material
what is inversion (structural)
-piece of chromosome INVERTS (top to bottom) -REVERSES its orientation and reattaches to original -two breaks in a SINGLE chromosome -PERICENTRIC= around the centromere -PARACENTRIC= away from centromere
what is translocation (structural)
- piece TRANSFERRED over to another chromosome
- segment BREAKS off and attaches to a non-homologous chromosome
- balanced translocation, robertsonian, isochromosomal