Lecture 17 Flashcards
what occurs in Cri-du-Chat syndrome?
part of chromosome 5 is deleted and missing genes required for normal development
what do we know about the genes lost in Cri-du-Chat syndrome?
none are haplosufficient –> all are haploinsufficient
2 possible causes of chromosomal deletions
- breakage + rejoining at incorrect place
- crossing over btwn repetitive DNA
what occurs in williams syndrome?
always caused by 1.5 Mb deletion on one homolog of chromosome 7
how does the deletion of Williams Syndrome occur?
region of 17 genes is flanked by PMS sequences
when the repeats pair in the wrong place during crossover, creates 2 unequal products: 1 with deletion, 1 with duplication
3 ways to detect chromosome deletions
- observe length/pairing
- DNA analysis with genomic technique
- complementation test
how can we use chromosome pairing to detect deletions?
sequences line up and will form deletion loop
what does the complementation test show if you cross a tester chr with recessive mutations and a WT chr?
will see WT phenotype –> WT genes complement for the recessive mutations
what does the complementation test show if you cross a tester chr with recessive mutations and a chr with WT alleles but some deleted?
will mutants of deleted genes
how can we use known deletions to map a recessive mutant allele?
cross tester with diff chr with deletions –> can map where certain recessive alleles are
what are large duplications known as?
segmental duplications
what does the size of the duplicated part depend on?
depends on how far apart the repeated sequences are
since we can see a lot of segmental duplications in the human genome, what does this indicate?
since duplications are caused by misalignment of repetitive sequences during crossover, having more duplicated sequences indicates that there is more misalignment
how do duplications impact an individual vs evolution?
duplication may be bad for individual but good for evolution
2 types of chromosome inversions
- paracentric –> does NOT include centromere
- pericentric –> includes centromere
what is the result of inversion if breakpoints are BETWEEN genes?
no genes are disrupted
if original was ABCD, product is ACBD
what is the result of inversion if there is only ONE breakpoint BETWEEN genes?
a gene is disrupted –> LOF
what is the result of inversion if there are breakpoints IN 2 genes?
gene fusion (can lead to functional gene)
when does inversion affect meiosis?
ALWAYS! even if genes not affected
what is produced during meiosis when there are inversions?
forms inversion loop
describe what happens to a PARACENTRIC-inversion heterozygote during meiosis
- crossover occurs in loop
- upon segregation in anaphase, forms dicentric chromosome and an acentric fragment that is lost
- breaks randomly btwn the 2 centromeres
- forms a normal product, 2 deletion products, and an inversion product
describe what happens to a PERICENTRIC-inversion heterozygote during meiosis
- crossover occurs in loop
- no dicentric chromosome bc pericentric, so no breaks involved
- forms 2 normal products (1 of each chr), 1 product with “a” duplication and “d” deletion, and 1 product with “d” duplication and “a” deletion
what are the clinical consequences of inversions on adults?
will still get some normal products so some daughter cells will be viable
gametes that inherit abnormal products/crossover chromosomes will be infertile bc cannot pair properly
- somatic cells will be normal bc don’t require pairing during mitosis
what are the effects of inversion on recombinant progeny?
if 2 genes are 45 mu apart, expect 45% of progeny are recombinant
but with inversion will see «45% bc of inviable products
what are the implications of having a larger inversion?
larger inversion
= higher chance of recombination within inversion
= more gametes with large duplications/deletions
= progeny don’t survive
