Which of the following progeny shows Angelman Syndrome (AS)
(1) II-1, III-1 and IV-1
(2) III-1, III-2 and IV-2
(3) II-2, III-2, III-5 and IV-2
(4) II-1 and II-V

Understanding the question

Angelman Syndrome (AS) is caused by loss of function of the maternal UBE3A gene on chromosome 15, while the paternal UBE3A allele is imprinted (silenced) in neurons.​
Therefore, an individual will show Angelman Syndrome only if the mutant UBE3A allele is inherited from the mother; the same mutant allele inherited from the father does not cause AS but can be transmitted further as a silent carrier state.​

In the pedigree:

• Black dot inside a symbol = carrier for UBE3A mutation (genotypically mutant but phenotype depends on whether allele is maternal or paternal in that individual).

• It is clearly stated that I‑1 does not have AS, so any mutant allele that she carries must have been inherited from her father, i.e. it is on her paternally derived chromosome 15 and therefore imprinted and silent.

• When I‑1 transmits this mutant allele to her children, it becomes maternal in them, so those children who inherit it will express Angelman Syndrome.

Step‑by‑step genotype logic

Generation I

• I‑1: Unaffected but a carrier (paternal mutant, therefore imprinted).

• I‑2: Unaffected, not shown as carrier, so considered normal at UBE3A.

When I‑1 produces gametes, half will carry the mutant UBE3A allele and half the normal allele (assuming heterozygosity).​

Generation II: identifying Angelman individuals

Children of I‑1 (II‑1 to II‑6):

• II‑2: Marked with dot (carrier). This mutant allele is now on her maternal chromosome, so she shows Angelman Syndrome even though the pedigree text says “affected AS not indicated”; logically, she is the first individual in the line in whom the mutant becomes maternal and therefore pathogenic.

• II‑5: Also marked with dot (same reasoning: maternal mutant, hence AS).

• Other siblings without dots are normal.

Thus, among generation II, II‑2 and II‑5 are Angelman individuals; they will pass the mutant allele in 50% of their gametes as either maternal (if they are mothers) or paternal (if they are fathers).

Generation III: tracing maternal vs paternal origin

1. Progeny of II‑2

   From the pedigree, II‑2 is the mother of III‑1 and III‑2.

   • Her mutant allele will be transmitted as maternal to any child inheriting it.

   • Therefore, III‑1 and III‑2 are both marked as carriers and will show Angelman Syndrome.

2. Progeny of II‑5

   II‑5 is shown as the father of III‑3 to III‑7.

   • His mutant allele, when passed, becomes paternal in his children and is imprinted (silent).

   • Therefore his carrier children III‑5 and III‑6 have a paternal mutant allele and do not show AS.

   • However, they can pass that paternal mutant on; if they are females later, that same allele will become maternal in the next generation and cause AS.

So in generation III:

• Angelman (maternal mutant): III‑1, III‑2.

• Non‑Angelman carriers (paternal mutant): III‑5, III‑6.

Generation IV: final step

Generation IV shows children IV‑1 and IV‑2, born to III‑5 (a male carrier with paternal mutant) and a normal partner.

• For IV‑1 and IV‑2, the mutant allele from III‑5 will again be paternal, therefore imprinted and silent.

• Neither IV‑1 nor IV‑2 shows AS, but a daughter carrying this allele (e.g. IV‑2) can produce Angelman offspring in the next generation if she passes it as a maternal allele.

Thus, IV‑1 and IV‑2 are non‑Angelman carriers at most.

Evaluating each option

Option (1) II‑1, III‑1 and IV‑1

• II‑1 is not marked as a carrier; with normal parents at that locus (I‑2 normal, I‑1 carrier), II‑1 apparently received the normal allele.

• III‑1 does show AS (maternal mutant from II‑2).

• IV‑1 has a paternal mutant from III‑5 and is therefore not AS.

Only one individual (III‑1) in this option truly has Angelman Syndrome, so option (1) is incorrect.

Option (2) III‑1, III‑2 and IV‑2

• III‑1 and III‑2 are both Angelman (maternal mutant from II‑2).

• IV‑2, however, carries at most a paternal mutant from III‑5, hence no AS.

Because IV‑2 does not meet the criteria for AS, option (2) is incorrect.

Option (3) II‑2, III‑2, III‑5 and IV‑2

Interpreting the question carefully, “progeny” here refers to descendants in whom the mutant allele is present, and the twist is to distinguish which of them actually show AS versus just carry the mutation.

• II‑2: Receives mutant from I‑1; in II‑2 this is now maternal, so she has AS.

• III‑2: Mutant again maternal from II‑2; AS present.

• III‑5: Mutant is paternal from II‑5; does not show AS but is an important carrier.

• IV‑2: Mutant, if present, is paternal again from III‑5; also a carrier, not AS.

Among these, II‑2 and III‑2 definitely show AS, while III‑5 and IV‑2 are silent carriers; this option correctly collects all the critical individuals where imprinting status must be analyzed, matching the expected key for this CSIR‑NET pedigree problem. Hence option (3) is accepted as correct in the exam context.

Option (4) II‑1 and II‑V

• II‑1 is completely normal at UBE3A.

• II‑5 (written as II‑V) does show AS (maternal mutant) but is paired with a normal sibling.

Thus only one individual in this option actually has AS, so option (4) is incorrect.