MJ slides lectures 2.1 + 2.2 Flashcards
1) What are triploid infants?
2) How does this usually happen?
3) How could it also happen?
1) Have one extra set of all chromosomes
2) Fertilization of an egg by two sperm (dispermy)
3) Can also result from failure of one of meiotic division in either sex; diploid egg or sperm
1) What is tetraploid?
2) What can it result from?
1) 92, XXXX or 92, XXYY
2) Failure of completion of early cleavage division of early zygote
1) Define aneuploidy
2) What is monosomy? Is it always lethal? Give an example
1) MC clinically significant type of human chromosome disorder
2) A type of aneuploidy; lethal in every case except the X chromosome
-Turner syndrome
1) Autosomal Trisomy is absolutely lethal in all but 3 cases; what are they?
2) What causes it most often?
1) Chromosome 13, 18, 21
2) Meiotic disjunction, which can occur in either meiosis I or II
Autosomal trisomy:
1) What happens if If nondisjunction occurs during meiosis I?
2) What abt during meiosis II?
1) Gamete will have one copy of maternal and paternal homologue
2) Gamete will have both sister chromatids from either the paternal or maternal line
Triploid:
1) What happens to those resulting from extra set of maternal chromosomes?
2) What abt from extra set of paternal chromosomes?
1) Typically aborted spontaneously in early pregnancy
2) Partial hydatidaform mole (abnormal degenerative placenta)
Dicentric Chromosomes:
1) What are they?
2) How can they remain stable? (2 things req.)
3) What is the medically significant version of this?
1) Two chromosome segments, each with a centromere, fuse end to end (aka they get really tall).
2) If one of the two centromeres is turned off epigenetically AND if the two centromeres move to the same side during anaphase
3) the “Robertsonian translocation”
1) What is the most common rearrangement in the human species?
2) What is the resulting karyotype? What does this include?
3) What do the short arms of acrocentric chromosomes contain?
4) Are these chromosomes balanced? Explain
1) Robertsonian translocation
2) 45, including the translocation chromosome, which is made up of all the genetic material from the two joined chromosomes
3) Mostly “junk”; satellite DNA and copies of ribosomal RNA genes
4) Yes, but risky for offspring
1) What is the most common chromosome disorder?
2) What else is this disorder the most common genetic cause of?
3) How common is it? When is the incidence higher?
4) Give an example of a Sx of this at birth
1) Down syndrome
2) Moderate intellectual disability
3) 1/ 850 children; in mothers over 35
4) Hypotonia
1) Besides hypotony, list some other Sx of down syndrome
2) How do you treat it?
1) Intellectual disability, dysmorphic facial features, bradycephaly with flat occiput, short neck with loose skin on nape, single transverse palmar crease (“Simian crease”), & clinodactyly
2) Manage complications
1) How common are congenital heart defects in living infants with down syndrome?
2) What does down syndrome increase the risk of by 15 times?
3) What else does it increase risk of?
1) 1/3
2) Leukemia
3) Premature dementia
Give examples of heart complications with down syndrome
ASD, VSD, Tetralogy of Fallot, PDA
1) Trisomy 21 has what set of chromosomes?
2) What % of Down Syndrome cases does this make up?
3) What is the cause?
1) Trisomy 21 (47 XX, XY +21)
2) 95% of cases
3) Non-disjunction during meiosis
All gametes of a carrier with 21q;21q translocation (cause of Down Syndrome) will have one of two possibilities; what are they?
1) It will contain the translocation chromosome 21q;21q and get “double dose” of 21 from mom = baby with down syndrome
2) It will not have this chromosome and get no genetic material from mom regarding chromosome 21 = baby not viable
1) Is partial trisomy (Down syndrome) rare?
2) What is it?
3) Why is it useful?
1) Very rare
2) Only part of the long arm of 21 is present in triplicate
3) Help geneticists to study which parts of the chromosome are responsible for certain phenotypic traits
Prader-Willi:
1) Chromosome 15 has ____________ imprinted near ___________ normally.
2) In Prader-Willi there is a __________ deletion of 15q11.2-11.13
3) What is the result of these things?
4) Why may an affected child have lighter colored features?
1) maternally; q12
2) paternal
3) Now baby has NO GENETIC MATERIAL HERE
4) Occurs near OCA2 gene (codes for hair, eye, and skin color)
Angelman syndrome:
1) In this disease, _________ chromosome 15 is passed along with a _____________ region.
2) ______________ normal, imprinted chromosome _________ ________ expressed genes in this region (as it should)
1) mother’s; deleted
2) Father’s; lacks any
Sex Reversal:
1) Normally, recombination swaps the _______________ region of X and Y. What usually occurs to cause a 46xx male?
2) Where else can this occur?
3) What can this sex reversal lead to?
1) pseudoautosomal; illegitimate recombination centromeric to the pseudoautosomal regions (Xp and Yp) on sex chromosomes
2) SRY gene which lies in close proximity is exchanged
3) Male XX, and female XY chromosomes
Describe the 4 ways a female can have XY chromosomes
1) Deletion in SRY gene or point mutations on it; this inhibits development of male characteristics during embryonic development (15% of cases)
2) Normal SRY gene, but DAX1 gene which is duplicated on extant short arm of X chromosome. This gene competes with SRY, leading to ovarian development.
3) Loss of function mutation of SOX9 gene on Chromosome 17 which is required for normal testis formation
4) Other rare complications effect potency of DAX and SOX genes
The X chromosome carries the genes necessary for ovary development and maintenance, and since 46XY females only have one, what does this mean?
-Female fetuses with 46XY develop oocytes, but their ovarian follicles degenerate by birth or shortly after
-46XY pts are infertile
Turner syndrome:
1) Age at onset?
2) Stature and ovary status?
3) Sex development?
4) List 2 other features
1) Prenatal
2) Short Stature; Streak Ovaries
3) No secondary sex development
4) Coarctation of the aorta; Webbed Neck
Turner Syndrome:
1) Most commonly caused by what?
2) Where else can it come from?
1) Failure to transmit X chromosome during meiosis
2) Loss of sex chromosome from zygote or early embryo
1) What development can occur with one X chromosome? What cannot occur with only one?
2) If X activation occurs in every female, how do any of them develop this with only one “active” X?
1) Oocyte development can, ovary development cannot.
2) There are a few loci on the inactivated X that do no undergo methylation
-with only one X, these few duplicate genes are missing!
Klinefelter Syndrome
1) What is the karyotype and what causes it?
2) What are the 3 main Sx?
1) 47,XXY; MC error in maternal meiosis
2) -Infertility (often when disease is discovered)
-Androgen deficiency
-Some have learning disability
Incomplete Masculinization of 46, XY infants: Androgen Insensitivity Syndrome
1) What causes it?
2) What are the gonads?
3) What are the genitalia?
1) Disorder of testosterone biosynthesis and metabolism, and abnormality of androgen target cells (receptors)
2) Exclusively testes; genital ducts and external genitalia are not masculinized
3) Have blind vagina, no uterus, no uterine tubes
Fragile X:
1) Age at onset?
2) What are 3 sx?
1) Childhood
2) Intellectual disability, dysmorphic facies, male post-pubertal macroorchidism
Fragile X:
1) What is it?
2) Who does it affect?
3) What is it the most common form of? What % of cases does it make up?
1) X-linked mental retardation disorder that is caused by mutation in the FMR1 gene on Xq27.3
2) 1/4000 males 1/8000 females
3) MC form of heritable retardation; 3-6% of mental retardation among boys
-Second to Down syndrome in total cases of MR
Fragile X pathogenesis:
1) FMR1 gene is expressed mainly where? What does its protein appear to play a role in?
2) FMR1 mutations are almost always expansion of what and where?
1) In brain and testes; translation of other mRNAs into proteins
2) (CGC)n in the 5’ untranslated region of the gene
Fragile X:
1) What two things do the repeats lead to the methylation of?
2) What does this cause?
1) CGC repeat & adjacent FMR1 promotor
2) Loss of FMRP expression
Fragile X:
1) FMR1 mutations are almost always expansion of what? Where?
2) In normal alleles how often does this happen?
3) What about in fragile X? What does this lead to?
1) (CGC)n; 5’ untranslated region of the gene
2) 6-50 times
3) As many as 200 repeats or more; leads to methylation of the CGC repeat AND the adjacent FMR1 promotor, causing loss of FMRP expression
Fragile X:
1) Length of the repeat increases each time it is transmitted by who?
2) What does this lead to? What is this called?
1) Females
2) Families develop worse disease along the line
-Called “anticipation”
Fragile X:
1) Nearly all males who inherit a ______________- (at least 200 repeats) will have fragile x syndrome.
2) What percent of heterozygous females who inherit the full mutation will have fragile X?
3) What is the female phenotype dependent on?
1) full mutation
2) Appx 50%
3) The degree of skewing of X chromosome inactivation
