Sex Chromosomes Flashcards
Size of X and Y chromosomes
X = 153 Mb, 195 known gene loci Y= 50 Mb and 13 known loci (4 in common with X)
What region do X and Y share?
Xpter/Ypter pseudoautosomal region (PAR1) 2.6 mb
Par2 at X/Yqter
What gene is present in PAR1
Shox gene
What happens regions of asynopsis on x and y at meiosis
Not tolerated at meiosis so form sex vesicles
Where is the x inactivation centre (XIST)?
Xq13
Disruption of what area of X is associated with gonadal dysgenesis?
Xp11.2-p22.1
Where is the X critical region?
Xq13-q26
Breakpoints in this region associated with gonadal dysgensis
Breakpoints in what area of the X critical region is not associated with gonadal dysgenesis?
Xq22
Where is the SRY gene? What does sry do?
Proximal to PAR on the short arm.
It is the testis determining factor (TDF)
Where is the gonadoblastoma specific region (GBY)?
Proximal Yq (just blow centromere)
Several genes associated with infertility
Features of distal Yq?
Heterochromatic block Non-coding Variable length Q banding and c band positive DAPI Bright on FISH
Incidence of turner?
1:2000- 1:5000
True or false: turner is associated with older mother?
False- associated with older father- often male X missing
Signs of turner in utero?
Cystic hygroma (excess fluid at nape of neck) Inter uterine growth retardation
Symptoms of turners in newborns
Small for dates
Lymphadema (excess fluid beneath the skin) of hands and feet
Symptoms of turner in childhood?
Short stature (98%)
High arched palate (82%)
Short neck/low hairline (80%)
Hypoplastic widely spaced nipples (78%)
Features of turners in adolescence ?
Short stature
Primary ammenorrhea
Delayed puberty
Most common cytogenetics for turner?
55% 45,X 25% 46,X, abnormal X 12-20% 46,X, i(X)(q10) 15% mosaic Numerical Structural
Classic Turner syndrome symptoms
20-30% congenital heart malformations
30-60% structural anomalies of kidneys
Streak ovaries
Infertile
45,X/46,XX phenotype
Taller
Likely secondRy amenhorrea rather than primary
May be fertile /subfertile
Phenotype of 45 x/ 46 x, i(x)(q10) or ring r(x)?
Less turner. Only short stature and gonadal dysgenesis
Mitotically unstable structural abnormality results in post zygotic generation of the 45,x cell line
What is phenotype of 45x /46x with marker of y origin.?
Female may be at increased risk of gonadoblastoma (benighted tumour that can turn malignancy)
Where is the gonadoblastoma gene found?
Proximal Yq. Critical region GBY has candidate gene TSPY
True or false: turner phenotype is less severe if Xist is absent
False: more sever if absent
Functional disomy!!!!
Treatment for turner?
Growth hormone treatment for height
Puberty- treat with oestrogen and progesterone
Fertility- oocyte donation- embryo transplant
If Y present - surgery to remove streak ovaries
Frequency of Klinefelter syndrome
1/500-1/1000
When do klinefelters usually present?
As adults with fertility issues
Occasionally as children with LD
Clinical features of klinefelters?
30%-50% gynaecomastia (increased breast carcinoma)
Infertility/azoospermia
Eunuchoid habitus (f minute body type)
IQ reduced relative to sibs
Common other chromosomal cases of male infertility
45 x/ 46 xy
Y structural abnormalities
Isodicentric y, r(y)
Robertsonian translocation (or other translocation especially involving Acrocentric)
Features of 47, XYY
1 in 840
Mild clinical manifestation
Tall, prominent forehead, maybe associated with behaviour problems
Normal fertility
Features of 47, XXX
1 in 1000 newborns
Essentially normal phenotype
Mild Devdel and motor delay wide variation
May have increased risk of having xxx or xxy offspring
48, xxxx
Iq 30-80 Normal to tall stature Speech delay Downs like features- epicanthic folds, midface hypoplasia Menstrual disorders, reduced fertility Additional Xs are maternally derived
49,XXxX
Moderate to severe MR
Prenatal onset growth deficiency
Microcephaly
Downs like features
48,xxxy
Moderate to mild Genital hypoplasia (reduced in size) Mild dismorphisms Normal height Usually additional xs from mother
49, XXXXY
Moderate to severe (iq 30) Low birth weight Short stature Hypogonadism Downs like features
What does the Shox gene do?
Short stature homeobox gene
Deletions found in idiopathic short stature
What disorder is caused by mutations in the shox gene?
Leri-Weill dyschrondrosteosis (lwd)
Characteristic by disproportionate short stature and a curving of radius (modelling deformity)
What is the mode of inheritance of mutations in the shox gene?
LWD - pseudoautosomal dominant disorder
Depends on genetic recombination between x and y
What disorder is caused by a homozygous loss of the SHOX gene?
Langer mesolmelic dysplasia (shortening of arms and legs =mesomelia)
Symptoms of Kallmann syndrome?
Anosmia (no smell) due to agenesis of the olfactory lobes
Hypogonadism secondary to deficiency of hypothalamic gonadotropin-releasing hormone (GnRH)
Mild MR
Colour blindness
2 forms of kallmann syndrome
1) AD due to LOF mutations in fibroblast growth factor receptor-1 (FGFR1)
2) sex linked form due to mutation in KAL1 close to PAR
Why is there a higher prevalence of Kallmann syndrome in males?
KAL1 partially escapes X inactivation
Where is KAL1 located?
Do
What is the cause of X-linked Icthyosis (lizard like)
Generalised scaling of the skin
Placental steroid sulfatase (STS) deficiency
What is the cause of x-linked icthyosis?
Complete o partial deletion of the STS gene mapped to Xp22.3
