genomic medicine

What is the difference in architecture between complex. Or mendelian diseases

In medelian

Even one signle mutation is enough

In complex

Polygenic and all the variants toghter coause it but none of those is sufficient alone

It is common to have low penentrance

Association study purpose?

Compare cases vs controls( people healthy)

It is to see if the risk allele frequency is high or not

But the coclusion you get is theta it may be associated with diseases susceptibility

BASICALLY IN COMPLEX IF YOU SEE “CAUSE” it’s wrong

In old studies what were “candidate gene association studies”

What discovery in 2003 allowed to have a new approch

Candiate= you have already a suspect gene for that disease

The human genome project that identified all the human genes and sequence the 3bln dna bp

What is GWAS

What is the difference with candidate association studies

What is collected from all the cases and controls?

Gwas is a genome wide association studies

Instead if having one gene suspected as in candidate stidy

You scan the whole genome!

You collect SNP all ( migliaia di milioni) from all the cases and controls and you can identify which region are associated with the diseases

What is the result of gwas

Fine map: you get the associated region

What are poligenic risk scores?

They take all the variants and put them in 1 risk score!

But again they mesuare a sPOSSIBILITY not a cause.

PRS limitations

Tipo i test online Su che predispozioni puoi avere

Predications in PRS may not be accurate for the individual butt overall for the population that is similar to the one studies

Many important thing as enviromental are not capture

What does popolutaion genetics studies

The genetic caracteristics of the population as a whole

Do the allele change or the gene in different population

Llele frewquency

Es. Abo group

Sicke cell + common where is malaria beacuse it was selected as a mutation that prevented malaria

Which are the migratory elements that allow the presence of new mutations

1. Founder effect

2. Selection

3. Isolation

4. Genetic drift

What doe sthe HARDY WEINBERG formula allow syou to see

Sll the different genotypes frequencie given allele b and a

Frequncy of aa, bb, and ab

Is (p+q) al quadrato

P2 è la frequenza di aa q2 bb e 2pq di ab

When is the poulation in HW equilibrium

When uou have the genotype freuqency that you had predicted

With the formula

What is the big limitation of H and W

That the formula does not chnage generation after generation so you have to assume that you always have the exacrt same freqency

Come calcoli il numero degli alleli

SE TU HAI 1419 individui

Il numero è il doppio!!!!! Non sbagliare! ( per fare la frequenza fai ration con tot degli alleli non della popolazione!)

What in the formula gives you incidence

Q al quadrato

and q is the allelilc frequency

For a recessive diseases where both parents are carrier the risk to get the disease for the child is

Carrier 1 risk x carrier2 riskx 1/4

In autosomal recessive the frequency of carrier is

2pq

If the disease is x linked how you define male p and female prob.

Mal= p and female you approximate at 2p

What is the risk formula for consanguineity?

Q2+fq

Q al quadrato is the normal piopulation risk which is usually extremely small for rare disease

F is the one for consaguinity! Which is always 1/16 per cugini di primo grado!!!