prenatal genetics Flashcards
Genetic terms
DNA- a macromolecule in which one of four bases (ATCG) bonds with deoxy ribose and a phosphate group, these nucleotides are strung together in in thin coiled strands in the shape of a double helix, DNA is responsible for the structure and function of living organisms
Gene- specific segment of DNA that are required for the production of a functional product
Chromosome- structural units consisting of chromatin and DNA that transmit genetic material from parent to offspring
Cell division
mitosis- reproduction of somatic (body) cells, allows the human body to grow, differentiate, and regenerate tissues
Meiosis- formation of germ (sex) cells, also gametes for sexual reproduction
Cell division meiosis review
1st chromosome pairs copy themsels to make duplicate pairs within the sex cells (egg or sperm)
Next the sex cell divides allowing the duplicated chromosome pairs to separate ( meiosis 1 )
Then the chromosome pairs themseves separate into idividual copies no longer pairs as the sex cells begin to divide again,
finally the sex cell from one parent contains a single copy of each chromosome to join with a single copy of each chromosome
Mistakes in meiosis - non disjunction
usually mistakes happen in meiosis 1
Nondisjunction - mistakes in the division and separation of chromosomes
One of the pair of chromosomes stay together and did not divide, the gray chromosomes correctly
The one that gets an extra chromosome and pairs up with a normal one –> trisomy (47
The one that loses the chromosome and pairs up with a normal one–> monosomy(45
clinical cytogenetic
Clinical cytogenetics is the study of chromosomes, in terms of their structure, number, and inheritance, in relation to medical genetics
Approximately 1/160 live births results in a chromosome abnormality while approximately 1 in 2 spontaneous miscarriages results from a chromosome abnormality
Chromosome disorders account for a substantial subset of prenatal, pediatric, and adult complications, including but not limited to miscarriage, still birth, birth defects, unusual facial characteristics and other dysmorphic features, cognitive deficiency, and tumor development
Ploidy
Euploid- normal number of chromosomes
Diploid- most human somatic (body) cells carry 2 copies of each chromosome, 23 chromosomes x 2= 46 chromosomes 2n
Haploid- reproductive cells carry half of the chromosomes within a somatic cell, 46 chromosomes/2 23 chromosomes
Abnormalities of chromosome number
Polyploid- a numerical deviation involving an exact multiple of the haploid number (n=23) triploid (69n,) tetraploid (92 chromosomes)
Aneuploid- a numerical deviation NOT involving an exact multiple of the haploid number- Trisomy (47), Monosomy (45)
Triploidy
Trploidy (3n) is a euploid complement of the standard diploid (2n) chromosome number in which there is a 3rd extra set of chromosomes - 69 instead of 46
Triploidy occurs in 1-3% of pregnancies, however it is lethal in virtually all cases, the prognosis depends on the parent of origin contributing to the extra set of chromosomes
Digynic triploidy
Caused by an extra chromosome set from mom
A digynic pregnancy has a small placenta while the fetus exhibits severe growth restriction
SMALL PLACENTA
These pregnancies are spontaneously aborted earlier in pregnancy
Diandric triploidy
diandric triploidy is caused by an extra chromosome set of paternal origin
A diandric pregnancy usually has an enlarged placenta while the fetus often is not growth restricted, this is referred to as a partial hyaditiform moe
Other than the risk to the fetus, women with partial molar pregnancies are at risk for severe early onset preeclampsia, hyperthyroidism, multiple theca lutein cysts, and gestational trophoblastic disease
Aneuploidy
Aneuploidy is NOT a euploid complement, but instead any other chromosome number that is not an exact multiple of the haploid chromosome number
Most common type of human chromosome disorder, aneuploidy has a pravelence of 5% among clinically recognized pregnanies
The risk for aneuploidy increases with maternal age, defined as 35 yo+ at the estimated dat of delivery in a singleton pregnancy - 1/385 for a woman who is 35 , risk of any 1/204
in a twin pregnancy advanced maternal age is defined as 33
Trisomy 21 (down syndrome)
Cognitive deficiencies, vision problems, hearing loss, thyroid dysfunction, increased risk for early onset dementia or cancer, and congenital anomalies, (heart malformations gastrointestinal abnormalities, the pravalence is 1/800 live births
trisomy 18 (edwards syndorom)
Limited to severe psychomotor delays, growth restriction, microcephaly, micrognathia, distinctive hand/ finger posturing and rocker bottom feet, and congenital anomalies, (Heart malformations, omphalacel, oral cclefting, clubfoot) the pravalence is 1/3000 live births
Trisomy 13 (patau syndrom)
Limited to severe psychomotor delays, microphalmia, polydactylu, and congenital abcormalities, hear brain
Monosomy X (Turner syndrome)
growth retardation, infertility with only 5% of patients experiencing spontaneous menstruation, hearing loss, possible cognitive disabilities, and congenital anomilies (heart malformations, cystic hygroma, horseshoe kidney and other renal abnormalities) the pravelece is 1/2500
Missing an X
XXY (klinefelter syndrome)
Tall/lean build, infertility, slightly delayed motor and language milestones, possible cognitive disabilities, increased risk to develop extragonadal germ cell tumor,, male breast cancer, Autoimmune disorders, the prevalence is 1/500-1000 live born males
translocation
A translocation is defined as a structuras breakage and rearrangement of chromosome material in a different composition
Reciprocal translocation- chromosome material is exchanged equally (balanced) or unequally (unbalanced)
robertsonian translocation- the short arms (p) of 2 chromosomes are lost and the long arms are joined(Q)
Translocations occur in approximately 1/375, they can occur spontaneosly or be transmitted from parent to offspring
Balanced vs unbalanced translocation
Chromosome translocations are described as either balanced or unnbalanced
Balanced- exchange of chromosome segments- nothing is deleted or duplicated, normal phenotype but have 5-10% risk of passing on an unbalanced chromosome to offspring
Unbalanced- chromosome segments that are deleted or duplicated, abnormal phenotypes (birth defects, unusual facial characteristics etc)
Deletion or duplication
Deletion- is the loss of a segment of chromosome, which may include any chromosome and any length/size, individuals with a deletion have a chromosomal imbalance (partial monosomy) and therefore the phenotype generally results from haploinsufficiency, or the inability of a single copy of a genetic unit to perform the function of two copies
Duplication- a duplication is the gain of a segment of chromosome, which may include any chromosome and any length/size, duplication are much more uncommon as compared to deletions, similarity to deletions- have a chromosomal imbalance
prenatal genetic screening
first trimester screen- a routine test for risk of fetal downsyndrome, trisomy 13, and trisomy 18, indicated for all pregnancy patients regardless of fetal aneuploidy risk
Cell free (cF) DNA- noninvasive prenatal screening (NIPS), a routine test for risk assessment of fetal down syndrome, trisomy 13, trisomy 18, and sex chromosome abnormalities, indicated for high risk patients
Maternal serum quad screen- routine test for down, trisomy 18 and nt defects, inidicated for all pregnanies
prenatal diagnositic
testing, CVS, amniocentesis, PUBS
environmental factors
Teratogens- Alcohol, Retinoic acid (isotretinoin), Valproic Acid
multifactorial inheritance
non mendelian inheritance combo of genetic and environment
pyloric stenosis (in males)
ancestry based carrier screening
Autosomal recessive, selected genes
CF and SMA, hemoglobinopathies
Tay sachs
Fragile X
mild to profound mental retardation, neuro stuff
