3 non-mendelian inheritance

Question 1

what is imprinting?

Answer 1

is a differential expression of a gene depending of whi gives the gene the mother or the father

Question 2

how many genes have been reported to have imprinted expression?

Answer 2

about 31

examples

prader willi

angelman syndrome

Question 3

what is prader-willi syndrome?

Answer 3

hypogonadism

obesity

mental retardation

hypotonia

1 in 10K

Question 4

hints that will point towards diagnosis of prader willi

Answer 4

• prenatal
  
  • decreased fetal movement
  • abnormal fetal position 40% breech
• Infancy
  
  • low normal birth weight
  • hypotonia
  • feeding problems
  • small penis, undescended testicles
  • thick sticky saliva
  • narrow forehead
  • short stature for genetic background

Question 5

what is the chromosomal abnormality in prader willi?

Answer 5

• chromosome 15
  
  • its and achrocentric chromosome
  • well seen with FISH technique
  • its a delition in chromosoma 15
  • ALWAYS the deletion comes from the DAD

Question 6

what is the disease caused by a deletion in chromosome 15 that comes from:

a) father
b) mother

Answer 6

a) from the father Prader Willi
b) from the mother: Angelman syndrome (stiff, jerky gait, absent speech. seizures and excessive laughter - called puppet children)

Question 7

what is angelman syndrome?

Answer 7

• deletion in chromosome 15
• comes from the MOTHER
• delayed neurodevelopment by 6-12 months
• speech impairment
• ATAXIA
• FREQUENT LAUGHTER
• FREQUEN SMILING
• HAPPY
• HAND FLAPPING
• excessive saliva
• SEIZURES
  *

Question 8

what % of prader willi have deletions?

what do the rest have?

Answer 8

• about 70% have deletions
• 25% maternal uniparental disomy
• 5% methylation defects
• <1% trabslocaiton on ch 15

Question 9

difference mitosis and meiosis

Answer 9

• Mitosis
  
  • occurs in somatic cells
    
    • results in 2 daughter cells with full chromosomes (diploid 46)
• Meiosis
  
  • occurs in gonads
  • results in haploid cells

Question 10

what is uniparental disomy?

Answer 10

when you inherit the TWO copies of a gene from only ONE PARENT

• this is an error in MEIOSIS
  
  • M1: heterodisomy
  • M2 ISOdisomy

Question 11

what is the meaning od disomy?

Answer 11

that a gametic cell is diploid instead of being haploid

• this is due to meiosis error
• can be heterodisomy (half from each parent)
• Isodisomy (both halfs from one parent)

Question 12

mechanisms of Uniparental disomy?

Answer 12

• trisomy rescue
• monosomy rescue
• gamete complementation

Question 13

whic is an example of contiguous gene syndrome?

Answer 13

Prader willi syndrome PWS

Question 14

what does methylation do to genes?

Answer 14

it silences them

Question 15

what is haploinssuficiency?

Answer 15

its when we make the protein but only half od the normal ammount

for ex these patients have fair hair

Question 17

what genetic test can you do for PWS or angelman syndrome?

Answer 17

methylation analysis

FISH

or PCR

Question 18

what would be good test for:

1. Deletion syndromes
2. UPD - uniparental disomy)
3. Imprinting

Answer 18

1. Deletion
   
   1. FISH
   2. MLPA (Duchene muscular dystrophy)
2. UPD
   
   1. SNP analysis
   2. microsatellite
   3. MLPA
3. Imprinting
   
   1. MEthylation analysis - for Prader willi
   2. Angelman (UBE3A mutaitons)

Question 19

whaqt is the recurrence risk for

1. deletions
2. methylation defects
3. chromosomal rearrangements
4. UBE3A mutations

Answer 19

1. deletion 1 in 1000
2. methylation defects — 50%
3. chromosomal rearrangements —- 50%
4. UBE3A ———–50%

Question 20

what are the diseases associated with very SHORT stature and very TALL stature?

Answer 20

very short = Achondroplasia (FGFR3 mutaiton)

very tall = Acromegaly (GNAS1, SSTR5 mutation)

Question 21

what is the main classification of genetic diseases?

Answer 21

1. chromosomal disorders (before birth)
2. single gene (from birth to puberty - peak early childhood)
3. polygenic (from birth to puberty - peak early childhood)
4. multifactorial (adulthood)

Question 22

• what type of genetic disorder is clefting?
• what is the frequency
• what types fo clefting are there?

Answer 22

• its multifactorial
• 1 in 700 babies
• types
  
  • cleft lip and palate (1 in 1K)
    
    • 50% of all clefts
    • 13% with other birth defects
    • more common in Asians less common in AA
  • Isolated cleft palate 1 in 2K)
    
    • 30% of all clefts
    • more in females
  • Isolated lip cleft
    
    • 20% of all clefts
    • more in males

Question 23

what are some characteristics of multifactorial traits?

Answer 23

• most parents are unaffected
• recurrence risk increases with # of affected children in a family
  
  • also increases with severity of disease
  • also with consanguinity

Question 24

• which test is the best to detect Prader will and angelman?

Answer 24

Methylation analysis!! (detects 99% of cases!!!)

FISH detects only 70% PWS and 80% angelman

Question 25

a couple are referred for genetic counseling after their son is Dx with PWS. What is the most likely molecular mechanism?

Answer 25

DELETION!!

Question 26

A disorder affects males twice as often as females. Which has the highest risk of being affected?

1. son of affected male
2. son of affected female
3. daughter of affected male
4. daughter of affected female

Answer 26

son of affected female!!!

because…

the question is saying that males are more often affected… so choose the SON option

female has higher liability