Block 4: Sfm 10/26 - Chromosomal Abnormalities

Front 1

What is a chromosome translocation?

Balanced vs unbalanced and effect on phenotype

Back 1

Chromosomal abnormality caused by rearrangement of parts between non-homologous chromosome.

Balanced: even exchange of material with no genetic information extra/missing; usually phenotypically normal

Unbalanced: exchange of material is unequal and results in duplications or deletions; usually result in mental retardation, congenital abnormalities in fetus

Front 2

What is the shorthand for:
Female with balanced translocation between chromosomes 5 and 8

Back 2

46, XX, t(5;8)

Front 3

How might an unbalanced translocation arise?

Back 3

Malsegregation during meiosis

Front 4

What normally occurs during meiosis I and meiosis II?

Back 4

Meiosis I: Aligned homologous chromosomes separate
Meiosis II: Sister chromatids separate

Front 5

What are the possible gamete outcomes when you have a translocation between two chromosomes?

Discuss gamete viability.

Back 5

When there's a translocation, derivative of chromosomes doesn't know which chromosome to pair up with.

If have a translocation between chromosomes 5 and 8, can get:

Adjacent segregation:
Derivative 8 and Chrom 5 in one gamete
Derivative 5 and Chrom 8 in one gamete
Derivative 5 and Chrom 5 in one gamete
Derivative 8 and Chrom 8 in one gamete

Will result in deletions and duplications in gametes. Gametes are ANEUPLOID usually NOT viable.

Or can get Alternate Segregation
Der 8 with Der 5
Chrom 8 with Chrom 5

Gametes are EUPLOID, and viable bc contain all of genetic information.

Front 6

Define following:

Metacentric Chromosome
Sub-Metacentric Chromosome
Acrocentric Chromosome

Back 6

Metacentric: Chromosome has equal arms (p = q)

Sub-metacentric: Centromere is located off chromosome center (p is short arm, q is long arm)

Acrocentric: Centromere is located near an end

Front 7

What is a Robertsonian Translocation?

Describe phenotype.
Affected chromosomes?
Effect on chromosome number?

Back 7

Occurs when long arms (q) of two ACROCENTRIC chromosomes fuse at centromere, resulting in loss of two short p arms.

p arms carry non-critical genes (some ribosomal genes)

Phenotypically normal, but are carriers of Robertsonian translocation.

Acrocentric chromosomes: 13, 14, 15, 21, 22

Reduces chromosome number to 45

Front 8

Decode:

45, XX,der(13;14)(q10:q10)

Back 8

45 chromosomes
female
Robertsonian Translocation between chromosomes 13 and 14
q's mean long arm is present

Front 9

What is a disomic gamete and how can it result in trisomic conceptions? Monosomy?

Back 9

Robertsonian translocations lead to gametes with TWO copies of a chromosome (DISOMIC gametes)

Meiosis can lead to trisomy of genes 13, 14, 15, 21

21--> DOWN SYNDROME
Most others miscarry.

Also leads to monosomy (gametes with only one copy of a chromosome and no copy of another chromosome)

Front 10

Do all babies with Translocation Down Syndrome have a parent who is a Robertsonian Carrier?

Back 10

No, both parents may hve normal chromosomes. Robertsonian translocation may have occured de novo in egg or sperm prior to fertilization.

Front 11

What are some causes of deletion? Are deletions fatal?

Back 11

Errors on crossover during meiosis
Chromosomal translocations
Crossover within an inversion
Breaking without rejoining

Large deletions usually fatal
Smaller deletions likely to be less fatal

Front 12

What is a haploinsufficiency?

Back 12

Loss of half of normal activity of a protein; causes disease/disorders of deletion

Front 13

What is a microdelection?

Back 13

Syndrome caused by deletion spanning several genes too small to be detected under microscope

Front 14

What are the symptoms of 22q11.2 deletion syndrome?

Back 14

Murmur, TETRALOGY OF FALLOT

Low calcium

Developmental Delays

Front 15

What is segmental aneuploidy?

Back 15

AKA Chromosomal Duplication

Front 16

What are some causes of chromosomal duplication?

Back 16

Unequal crossing over between two homologous chromosomes/chromatids

Crossing over in inversion loop during meiosis...

Front 17

What is Charcot Marie Tooth Disease? Cause?

Back 17

Most common inherited peripheral neuropathy disorder; slowly progressive atrophy of distal muscles

Due to DNA duplication in region p17.2-p12 of CHROMOSOME 17 (gene that encodes myelin)

Front 18

What's an inversion?

Paracentric vs Pericentric?

Back 18

Inversion - Breakage and rejoining of segments within the chromosome

Paracentric: breakage and reunion within same arm (doesn't involve centromere)

Pericentric: breakage and reunion on either side of the centromere (involves centromere)

Front 19

What are the clinical consequences of inversions?

Back 19

If inherited 'as is', no clinical consequences

If cross over within inversion area during meiosis, gametes will contain unbalanced karyotypes (leads to spontaneous loss)

Front 20

Dicentric vs Acentric Chromosomes

Back 20

Dicentric = two centromeres
Acentric = no centromere

Front 21

What would crossing over of a paracentric inversion result in?

Back 21

Dicentric and acentric chromosomes

Gametes not viable

Front 22

What would crossing over of a pericentric inversion result in?

Back 22

Viable gametes but results in duplications and deltions in chromosome involved

Risk for abnormal pregnancy is higher

Front 23

Is it possible for a balanced translocation to result in a normal phenotype?

Back 23

Yes, as long as patient has all genetic material.

Front 24

A 31 year-old woman consults a fertility clinic after having two miscarriages. Chromosomal analysis reveals a paracentric inversion.

Should the woman be worried that this inversion will result in abnormal birth outcomes?

Back 24

No--in the case of paracentric inversions, crossing over in the inversion loop results in NON-VIABLE acentric or dicentric gametes.

Front 25

What type of chromosomes can result in a Robertsonian translocation?

Back 25

Acrocentric

Front 26

What type of translocation is this:

45, XX, der (13;14)(q10;q10)

Back 26

Robertsonian

Results in one fewer chromosomes; only occurs between acrocentric chromosomes (13, 14, 15, 21, 22)

Front 27

A woman is told that she has a Robertsonian translocation between chromosome 14 and 15. She is worried about having an abnormal birth outcome.

What is the probability of her having a child with a trisomy?

Back 27

0%: fetuses with trisomy 14 and/or trisomy 15 are non-viable. Mother, however, will be at increased risk for miscarriages.

Front 28

Type of inversion?

Back 28

Pericentric (involves centromere)