a second practice problem set (with answers) is on the course website. the review session for the...
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![Page 1: A second practice problem set (with answers) is on the course website. The review session for the second midterm is on Thursday evening, April 10, from](https://reader036.vdocument.in/reader036/viewer/2022062407/56649f585503460f94c7de90/html5/thumbnails/1.jpg)
A second practice problem set(with answers)
is on the course website.
The review session for the second midtermis on Thursday evening, April 10, from 7-9pm
in ROOM 141 GIANNINI HALL
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mentioned GSD via a Maternal Effect system(for a blowfly)
progeny: m/m, m/+, or +/+
progeny: m/m, m/+, or +/+
progenyphenotype
mutant
progenyphenotypewildtype
Genotype of mother
determines (or at least influences) thePhenotype of the progeny
Strict maternal effect (only mother can supply the needed + gene product)
mother: m/mvs.m/+
determines
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mentioned GSD via a Maternal Effect system(for a blowfly)
progeny: m/m, m/+, or +/+
progeny: m/m, m/+, or +/+
progenyphenotype
mutant
progenyphenotypewildtype
progeny:m/morm/+, or +/+
progeny phenotype mutant
progeny phenotype wildtype
progeny: m/m, m/+, or +/+
progenyphenotypewildtype
Genotype of mother
determines (or at least influences) thePhenotype of the progeny
Strict maternal effect (only mother can supply the needed + gene product)
Rescuable maternal effect (either mother or progeny can supply + gene product)
mother: m/mvs.m/+
mother: m/mvs.m/+
influences
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Are male X-linked genes turned UPor are
female X-linked genes turned DOWN?
Giant Polytene Salivary-Gland Chromosomes
X chromosome 2800 genes
measure rate of RNA precursor incorporationinto “nascent” transcripts (during interphase)
…average transcription rates (per unit DNA)
X-chromosome dosage compensation in Drosophila:
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transcription rate for Male X-linked genes are turned UPrelative to autosomal or female X-linked genes
X chromosome 2800 genes
average transcription rates (per unit DNA):
female X = female autosomes = male autosomes < male X
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What phenotype would one expect for mutationsthat disrupted genes that encode the machinery
for X-chromosome dosage compensation?
needed (only) for hyper
needed (only) to prevent hyper
male (X:A=0.5)-specific lethal
female (X:A=1)-specific lethal
Normal gene function: Phenotypic consequencesof loss by mutation:
Female: XX Male: XY
no X hyperactivation X hyperactivation
That is how the relevant genes are recognized
(MSLs encode protein complex on male X)
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Fig. 18.23 (p675)
Among the genetic pathways that control development,those controlling sexual development are perhaps the best understood.
Sxl controls sex determination; dsx controls sexual dimorphism
also dosagecompensation
SxlConstitutive is male-specific lethal
Sxlnull is female-specific lethal
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What about worms? (C. elegans)
XX AA X AA
hermaphrodites(females that make sperm)
males
(1) both hermaphrodite X’s active
(3) at the transcriptional level
(2) male X twice as active as each hermaph. X
(4) hermaph.-specific lethal genes encode protein complex on hermaphrodite X’s that turns transcription down
fly male-specific lethal genes encode protein complex on male X that turns it up
(like the fly)
(like the fly)
(like the fly)
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How do we mammals dosage compensate?
OneBarr Body
NoBarr Body
XOAA Turner females
XXYAA
Kleinfelter males
XXXXAA (mentally retarded) females
No Barr Body
One Barr Body
Three Barr Bodies
XYAA
females males
XXAA
“sex chromatin”First clue:
#BB = #X-1
Barr Body rule:
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Odd behavior of an X-linked mammalian gene:
Individual blood cells arephenotypically either
G6PD+ or G6PD-
only one or the other X-linked allele seems to be active
in any given blood cell
Another clue:
G6PD+/G6PD-:heterozygote
not what we saw with the eye of the w+/w- fly
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Geneticist Mary Lyon:
#BarrBodies = #X-1
Observations:
Hypothesis:
(2) Dosage compensation by inactivation of all but one X chromosome
XYAA
malesfemales
XxAA
females
XxxxAA
(1) Barr Body = inactivated X chromosome
x
Barr Body
mosaic expression of G6PD+ (on X)
mosaic c+ expression when c+ on X
(translocation of autosomal coat color gene c to X)
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X-chromosome inactivation:
(1) initiated very early in development
(2) generally random in embryo proper (paternal = maternal)
(3) once initiated, stably inherited
(4) reactivation of inactivated X occurs in germ cells during oogenesis
Xmaternal Xpaternal
(often paternal in extra-embryonic)
an epigenetic phenominon
(at ~500 cell stage in humans)
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Striking human example of X inactivation in action:
Anhidrotic Ectodermal Dysplasia (EDA):
hemizygous males (EDA-/Y) & homozygous females (EDA-/EDA-)
no sweat glands (incl. breasts)
missing & abnormal teeth/hair
EDA+/EDA-
PHENOTYPICMOSAICS
cell autonomous trait
Identical twins:
little skin cell mixing during developmentPatchiness signifies
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…are all non-functional X-linked alleles (a-) semi-dominant?
For X-linked genes: If a+/a- mammals are functional mosaics of a+ & a- cells
NO
(1) perhaps not cell autonomous (and 50% a+ function is sufficient for normal phenotype)
(2) perhaps cell autonomous, but deleterious early--- abnormal cells selected against (they may be outcompeted by normal cells)
how is a phenotype related to a+ gene expression?Need to know for gene a:
(dominance depends on how phenotype is operationally defined)
consider hemophilias
Most animals compensate well for cells lost during development
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X2matX2pat 50:50 mat vs. pat active
X1matX2pat
X2matX1pat
Mapping the source of the inactivation bias defined Xce
the genetics of the X controlling element
X1matX1pat 50:50 mat vs. pat active
65:35 mat (1) vs. pat(2) active
35:65 mat (2) vs. pat(1) active
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almost allgenes in cis
shut off
Study of T(X,A)s in mouse tissue-culture cells defined theXic (inactivation center)
(“source” of inactivation in cis)
Study of variations in “X inactivation strength” (in whole mice)defined the
Xce (controlling element)(determines chromosomal inactivation competativeness)
Xic = Xce
Xc+
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Xic = Xce
The source of a very odd RNA :
X-inactivation-specific-transcript:
Xist
(number of) (s)
…a non-coding RNA from the inactive X that coatsthe inactive X chromosome in cis
one of the first examples of a regulatory RNA
X
X
X
X
X
X
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X
X
Consequences of deleting Xic (source of Xist):
always the active X
Xist RNA
X
X
Xist RNA
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Xist transgene (inducible) on autosomewill coat autsome with Xist and silence it
…but only during an early window of time