Disordini genomici
Lezione 14
By NA
DUPLICAZIONI SEGMENTALI LCR
distal
CMT1A-REP
proximal
CMT1A-REP
LCR17pE
~31Kb
PMP22
24Kb
distal
SMS-REP
middle
SMS-REP
proximal
SMS-REP
LCR17pG
~31Kb
LCR17pF
~33Kb
LCR17pA
383Kb
LCR17pB
191Kb
LCR17pC LCR17pD
191Kb
91Kb
~200Kb
7,4 Mb totale LCR 1,7 Mb (23%)
By NA
CEN
DUPLICAZIONI SEGMENTALI LCR
7q11.23
Inversione benigna nel 28% dei genitori
crom.7
ELN
cen
C
A
B
tel
C
B
A
A
C
tel
cen
C
B
A
B C B
A
cromosoma deleto
cen
A
C
cromosoma invertito
C
By NA
B
A
B
C
A
B
B
A
C
tel
DUPLICAZIONI SEGMENTALI LCR
F8
C
tel F8A F8A
CpG
Cen
F8A
1
F8B
22
23
26
F8A
F8A
tel
22
F8
C
1
F8A
CpG
F8B
Cen
F8A F8A
F8A
By NA
23
26
P.Stankiewicz and J.R.Lupski
Genome architecture, rearrangements and genomic
disorders
TRENDS in Genetics Vol. 18: 74-82, 2002
Banter syndrome type III
Gaucher disease
Fam. juv. nephronophthisis
Fascioscapulohumeral muscular dystrophy
Spinal muscular atrophy
Cong adrenal hyperplasia (21 hydroxylase def.)
Glucocorticoid-remediable aldosteronism (GRA)
Beta-thalassemia
alfa-thalassemia
Polycystic kidney disease 1
Charcot-Marie-Tooth (CMT1A)
Her. neur. with liability to pressure palsies (HNPP)
Neurofibromatosis type 1 (NFl)
Pituitary dwarfism
CYP2D6 pharmacogenetic trait
Ichthyosis
Red-green color blindness
Incontinentia pigmenti
Hemophilia A
Emery-Dreifuss musc. dystr.
Hunter syndrome
By NA
Disordini genomici
1p36
1q21
2q13
4q35
5q13.2
6p21.3
8q21
11p15.5
16p13.3
16p13.3
17p12
17p12
17q11.2
17q23.3
22q13.1
Xp22.32
Xq28
Xq28
Xq28
Xq28
Xq28
By NA
By NA
SD (in omozigosi)
CNV
Assenza di dati
per questioni tecniche
By NA
DNA da testare
By NA
DNA da testare
By NA
By NA
By NA
By NA
Duplicazioni segmentali
comparazione uomo-scimpanze'
- comuni: 66% (79.8Mb)
- scimpanze'-specifiche (11.4Mb)
- umano-specifiche: 33% (26.5Mb)
By NA
Nature 444:444-454 (2006).
Nature 453:56-64 (2008).
Differenza media fra 2 individui: circa 20.000.000 bp
By NA
By NA
Il significato?
By NA
plasticity
=
variability
=
evolution
perfezione
=
nessuna prospettiva
evolutiva
By NA
fixed CNV (SD)
CNV
By NA
fixed CNV (SD)
CNV
after meiosis
before checkpoint
By NA
PNAS 104:10950-5 (2007).
… Finally, the high level of instability at the alpha-globin locus
contrasts with the rarity in most populations of chromosomes
carrying duplications or deletions, pointing to strong selective
constraints that maintain alpha-globin gene copy number in
human populations.
By NA
PNAS in press
Li-Fraumeni syndrome is an autosomal dominantly
inherited disorder characterized by a strikingly increased
risk of early-onset breast cancer, sarcomas, brain tumors
and other neoplasms in individuals harboring germline
TP53 mutations.
By NA
By NA
Science 320: 539-543, 2008
By NA
Am J Hum Genet 81: 1057-1069, 2007
Nature Genet 40:1076-1083, 2008.
By NA
PNAS 105:16221-16226, 2007
By NA
Variabilita’ ricchezza per la specie
Variabilita’ problemi per i singoli
By NA
E’ la logica :le esigenze dei molti
contano di piu’ di quelle dei pochi
o di uno
Mr.Spock: Star Trek : L’ira di Khan
By NA