Genetics (week 1): Intro and on Chromosomes, Trisomy 21
OMIM HOME: http://www.ncbi.nlm.nih.gov/omim
this is the most imp reference for this discline
the genetic basis of everything even the photic sneeze
no longer in print form
contains 6 digit number for every genetic condition known for humans
first digit indicates mode of inheritance:
1 = autosomal dominant
2 = autosomal recessive
3 = x-linked
4 = y linked
5 = mitochondrial loci
6 = autosomal loci
our class is organized around these same categories
Kaminsky lecturing
computer programs for family tree mapping: genetics vs geneology
he uses cyrillic 2, it's pricy but best in his opinion
all programs are difficult to use, steep learning curve
long rant about ethics
amniocentesis question when parents plan to abort a female
didn't take notes on overview
chromosomes
most coiled up form of DNA
made of two chromatids connected at the centromere
short arm is "p", long arm is "q", numbering of regions outward from centre
humans are diploid
23 homologous pairs, one set from each parent: maternal and paternal homolog
22 pairs are autosomes, each is independent from each other (and orig thought from gender)
1 pair sex xsomes, X or Y
46 total
standard karyotype is pasteup of same set of xsomes by species
karyotype abbreviated as # then sex then derangements
I am 46XX with no known derangements
the Denver system, 1960
5-6 ish classifications
id by 1) size: lower numbered ones are larger, smallest is #22
by 2) centromere position: submetacentric, metacentric, acrocentric
centromere is never exactly in the center; even metacentric xsms have p and q arms
some (13-15, 21-22) have satellites
A = 1-3, long large metacentric
B = 4-5 acrocentric, etc
-->first karyotype displays
the Paris conference system
adds id by staining of bands
now can color code bands, allows better sorting
banding variability has been difficult to see via computers but they can now
International System of Human Chromosome Nomenclature
using banding, though bands are not genes
used today to ID most chromosome abnormalities
can id major and minor (pushing it) deletions, duplications, larger rearrangements, translocations
8q32 = xsme 8 on long arm (q) in region 3 band 2
too crude to ID many important diseases
CHROMOSOMAL DEFECTS
complete set = euploidy
1 complete haploid set of 23 found in human gametes (N)
2 complete sets found in regular diploid somatic cells (2N)
deletions of entire xsomes generally not compatible with life
aneuploidy = incomplete set
monosomy = 2N-1 (missing just one xsome --> 45) mostly nonviable
trisomy = 2N+1 (one extra --> 47) more viable than monosomy
there are no autosomal monosomies common enough to worry about
trisomies that occur: 21, 18 & 13
TRISOMY 21 = DOWN'S SYNDROME
"mongoloid idiocy"
most common trisomy, 1 in 800 live births
higher incidence with older mothers, in utero survival is minimal
est: 25% of all miscarriages dt trisomy 21
350,000 living people with it in US
47,XX,+21
accounts for ~33% of all moderate and severe mental retardation in children
sx: distinctive facies*, oblique palpebral fissures*, epicanthic folds, low nasal bridge, protruding tongue, small round head with flat occiput, low set ears, speckling iris, short stature/hands, broad neck, congenital heart dz (40-50%, serious in fewer who often die young), "simian" line in dermatoglyphics (single palmar crease, not double), premature aging, high incidence of leukemia (10-30x normal risk, about 2% of all child leuk), alz in almost 25% esp early onset
neuro sx: neonatal hypotonia, mental retardation (IQ 20-50), hearing/visual impairment in >50%
tx: needs intensive care, nurturance
prog: can live relatively normal life, expectancy is about 55 years but variable
this is the most imp reference for this discline
the genetic basis of everything even the photic sneeze
no longer in print form
contains 6 digit number for every genetic condition known for humans
first digit indicates mode of inheritance:
1 = autosomal dominant
2 = autosomal recessive
3 = x-linked
4 = y linked
5 = mitochondrial loci
6 = autosomal loci
our class is organized around these same categories
Kaminsky lecturing
computer programs for family tree mapping: genetics vs geneology
he uses cyrillic 2, it's pricy but best in his opinion
all programs are difficult to use, steep learning curve
long rant about ethics
amniocentesis question when parents plan to abort a female
didn't take notes on overview
chromosomes
most coiled up form of DNA
made of two chromatids connected at the centromere
short arm is "p", long arm is "q", numbering of regions outward from centre
humans are diploid
23 homologous pairs, one set from each parent: maternal and paternal homolog
22 pairs are autosomes, each is independent from each other (and orig thought from gender)
1 pair sex xsomes, X or Y
46 total
standard karyotype is pasteup of same set of xsomes by species
karyotype abbreviated as # then sex then derangements
I am 46XX with no known derangements
the Denver system, 1960
5-6 ish classifications
id by 1) size: lower numbered ones are larger, smallest is #22
by 2) centromere position: submetacentric, metacentric, acrocentric
centromere is never exactly in the center; even metacentric xsms have p and q arms
some (13-15, 21-22) have satellites
A = 1-3, long large metacentric
B = 4-5 acrocentric, etc
-->first karyotype displays
the Paris conference system
adds id by staining of bands
now can color code bands, allows better sorting
banding variability has been difficult to see via computers but they can now
International System of Human Chromosome Nomenclature
using banding, though bands are not genes
used today to ID most chromosome abnormalities
can id major and minor (pushing it) deletions, duplications, larger rearrangements, translocations
8q32 = xsme 8 on long arm (q) in region 3 band 2
too crude to ID many important diseases
CHROMOSOMAL DEFECTS
complete set = euploidy
1 complete haploid set of 23 found in human gametes (N)
2 complete sets found in regular diploid somatic cells (2N)
deletions of entire xsomes generally not compatible with life
aneuploidy = incomplete set
monosomy = 2N-1 (missing just one xsome --> 45) mostly nonviable
trisomy = 2N+1 (one extra --> 47) more viable than monosomy
there are no autosomal monosomies common enough to worry about
trisomies that occur: 21, 18 & 13
TRISOMY 21 = DOWN'S SYNDROME
"mongoloid idiocy"
most common trisomy, 1 in 800 live births
higher incidence with older mothers, in utero survival is minimal
est: 25% of all miscarriages dt trisomy 21
350,000 living people with it in US
47,XX,+21
accounts for ~33% of all moderate and severe mental retardation in children
sx: distinctive facies*, oblique palpebral fissures*, epicanthic folds, low nasal bridge, protruding tongue, small round head with flat occiput, low set ears, speckling iris, short stature/hands, broad neck, congenital heart dz (40-50%, serious in fewer who often die young), "simian" line in dermatoglyphics (single palmar crease, not double), premature aging, high incidence of leukemia (10-30x normal risk, about 2% of all child leuk), alz in almost 25% esp early onset
neuro sx: neonatal hypotonia, mental retardation (IQ 20-50), hearing/visual impairment in >50%
tx: needs intensive care, nurturance
prog: can live relatively normal life, expectancy is about 55 years but variable