cytogenetics 2

genetics

imprinting

expression of some genes is determined by parental origin of the allele

in imprinting the expression in the zygote/offspring is:

mono-allelic (expressed only from the maternal or paternal chromosome)

what is the imprinting control region

cpg islands that regulate expression of clusters of imprinted genes. use a combination of methylation and expression of non-coding RNAs to regulate transcription of protein encoding genes

dna methylation can silence what and what

can silence directly at a genes regulatory region to silence the gene OR can silence at an ICR (which usually silences a gene) to stop the lncRNA from silencing the gene so the gene is expressed.

what loci is involved in Prader-wili-syndrome

15q

in prayer-wili syndrome, are the genes silenced in the maternal or paternal germline

silenced in the MATERNAL germline

how common is PWS

1 IN 10000

causes of PWS

Paternal deletion in genes of 15q OR maternal UPD of chromosome 15 (carriers will have a maternal deletion of the genes on 15q)

what is PWS’s “opposite” syndrome

angelman syndrome

what loci is involved in angelman syndrome

15q (same as PWS)

Is the genes in angelman syndrome silenced in the maternal or paternal germline

silenced PATERNAL germline

how common is angelman syndrome

1 in 10000

causes of angelman syndrome

maternal deletion of the genes on 15q OR paternal UPD of chromosome 15 (carrier would have a paternal deletion of the genes on 15q)

what loci are involved in Beckwith-wiedermann syndrome

p15 region of chromosome 11

in BWS are the loci involved silenced in the maternal or paternal germline

silenced in the PATERNAL germline

how common is BWS

1 in 14000

what symptoms does BWS cause

basically an overgrowth in tissues

mechanisms that cause BWS

UPD paternal ch 11, loss of maternal CDKN1C, excess of paternal IGF2

What are the 2 noncoding regulatory RNA (lncRNA) involved in BWS

KCNQOT1 and H19

What are the 2 protein encoding genes involved in BWS

IGF2 and CDKN1C

what lncRNA and protein encoding gene is expressed only paternally in BWS

IGF2 and KCNQO1

What lncRNA and protein encoding gene is expressed only maternally in BWS

CDKN1C and H19

What does IGF2 do and in what Imprinting control region

IGF2 encodes insulin like growth factor that PROMOTES GROWTH of fetus. IC1

What does CDKN1C do and in what icr?

inhibits cell cycle progression: CONSTRAINS GROWTH. IC2

What does H19 do and what ICR

maternal: h19 is hypomethylated and EXPRESSED and suppresses IGF2 (suppressing growth)

Paternal: h19 is methylated (silenced) and IGF2 is expressed

IC1

What does KCN1OT1 do and on what ICR?

Maternal: it is methylated (silenced) and allows CDKN1C to be expressed

Paternal: it is hypomethylated and expressed, supressing CDKN1C expression

IC2

What protein encoding gene is involved with KCNQOT1

CDKN1C

What protein encoding gene is involved with H19

IGF2

What is BWS’s opposite disorder

silver-russel syndrome

what loci are involved in silver-russel syndrome

chromosome 11, 15p

what does silver-russel syndrome cause

dwarfism

causes of silver-russel syndrome

-hypomethylation of H19 leading to H19 expression and then suppression of IGF2

-MUTATIONS REDUCING IGF2 EXPRESSION CAUSES IT

(there are other cases not linked to ch11, all involved methylation levels)

what is the parental conflict hypothesis

it hypothesizes why mono-allelic expression occurs: mother benefits from constraining growth and father benefits from success of the offspring aka promoting growth

what are the chromosomal rearrangements

deletions, duplications, inversions, translocations

what do chromosomal rearrangements result from

errors in DNA repair or recombination (breaks in chromosome not repaired correctly or recombination between mis-paired chromosomes

which chromosomal rearrangement is the worst and why

deletions because it is the only one that completely LOSES the genes

which chromosomal rearrangements can be phenotypicaly normal in carriers as long as important genes aren’t disrupted

balanced translocations and inversions (unless translocation occurs from X chromosome to an autosome, this would affect gene dosage)

translocations can cause problems with what during meiosis

chromosome seperation

in translocation during recombination, instead of a bivalent a what occurs

tetravalent/quadrivalent (forms with 2 normal chromosomes and 2 derivative chromosomes. 4 chromosomes separating causes issues as there are a number of ways they can disjoin and this can result in a gain or loss of chromosome or parts.

instead of a bivalent what occurs during meiosis for a robertsonian translocation

a trivalent can form. when it splits and goes to poles this can cause monosomes and trisomies

do inversions increase the likelihood of chromosomal rearrangements during meiosis

yes because homologous regions are flipped.

what is a paracentric inversion

an inversion that does not include the centromere

what is a pericentric inversion

an inversion that DOES include the centromere

what are the possible outcomes for a paracentric inversion

1 wildtype chromosome

1 inverted chromosome

1 dicentric chromosome (two centromeres) NOT VIABLE

1 acentric chromosome (no centromeres) NOT VIABLE

What are the possible outcomes for a pericentric inversion

1 wildtype chromosome

1 inverted chromosome

2 chromosomes with deletions and duplications