Chromosomes/Genome Flashcards
Nondisjunction of __________ during Meiosis I will lead to 4 daughter cells with what n count
n -1, n-1, n+1, n+1
100% aneuploidy
Nondisjunction of __________ during Meiosis II will lead to 4 daughter cells with what n count
n, n, n+1, n-1
50% aneuploidy
p and q arms of the chromosome are ____ and ____, respectively
short (petit), long.
Chromosomes are numbered ________ from the centromere. Proximal and distal are relative to the _______.
Outward (proximal—>distal); centromere
Aneuploidy
Loss or gain of certain chromosomes
e.g. trisomy 21 or monosomy X
Polyploidy
Extra copies of all chromosomes e.g. triploidy (3n) or tetraploidy (4n)
46,XX,del(5p) syndrome is _____
Female with cri du chat syndrome due to deletion of part of short arm of one chr. 5 (del = deletion)
46,XX,dup(1)(q22-q25)
Female with duplication of sequences from q22-q25 on chromosome 1
46,Y,fra(X)(q27.3) Syndrome _____
Male with fragile X chromosome (fra = fragile)
46,X,i(Xq)
Female with isochromosome for the long arm of the X chromosome (i = isochromosome; duplication of p or q arms, in this case 2 q arms of X)
46,XX,ins(2)(p13q21q31)
An intrachromosomal insertion of segment 2q21-q31 into breakpoint at 2p13.
46,XY,inv(3)(p25q21)
Pericentric inversion of chromosome 3
47,XX,+21 Disorder ______
Female with trisomy 21 (+ = gain of)
Triploidy is most commonly caused by ______, but can be caused by ______ or _______.
Dual fertilization between 2 sperm, each with n ploidy; 2n ovum; 2n sperm
Tetraploidy results from _______
Endomitosis (DNA duplication w/o cell division)
What is the most common pathway for aneuploidy?
Nondisjunction during maternal meiosis
What is the terminalization hypothesis?
Explanation for the maternal age effect. Meiosis I arrest initiated in oocytes in fetal ovary—>Loss of cohesin allows movement of chiasmata toward the ends of homolog pairs Result: Precocious separation of homologous chromosomes, known as meiosis I nondisjunction
Normal or deficient growth • CNS abnormalities – holoprosencephaly – severe intellectual disabilities • Facial clefts • Polydactyly • Renal dysplasia • Congenital heart disease • Omphalocele • Dermal defects
Trisomy 13: Patau syndrome
Growth retardation Hypertonicity clenched hands narrow hips CNS abnormalities posterior fossa anomalies severe intellectual disabilities seizures Congenital heart disease
Trisomy 18: Edwards syndrome
Hypotonia • Dysmorphic features – characteristic facies – short fingers, transverse palmar crease – clinodactyly – wide “sandle gap” • Congenital heart disease • Gastrointestinal abnormalities • Early onset Alzheimer disease
Trisomy 21: Down syndrome
Phenotypes include tall stature, hypogonadism, under- developed secondary sexual characteristics, gynecomastia, usually infertile, some degree of language impairment.
Klinefelter Syndrome (47, XXY)
47,XYY
Jacob’s syndrome
• Speech delays
• Developmental delays
• Behavioral and emotional difficulties • Autism spectrum disorders
• Tall stature
Incidence is 1/1000 live male births, results from errors in paternal meiosis II, producing YY sperm.
• Not associated with criminality, as was originally hypothesized
Phenotypes include short stature, webbed neck, edema of hands and feet, broad shield-like chest, renal and cardiovascular anomalies, and a failure in ovarian development.
Turner Syndrome (45,X)
Mosaicism
A zygote containing two cell lines which differ in chromosome number. commonly caused by nondisjunction in an early post- zygotic mitotic division
Polyploid mosaic vs Aneuploid mosaic
e.g. diploid / triploid; e.g. normal / trisomy 21
Metacentric
the centromere is located in the middle of the chromosome, such that the two chromosome arms are approximately equal in length.
Submetacentric
the centromere is slightly removed from the center.
Acrocentric:
the centromere is near one end of the chromosome.
46,XX,ins(2)(p13q21q31): describe meaning
An intrachromosomal insertion of segment 2q21-q31 into breakpoint at 2p13
Balanced structural chromosomal abnormalities Definition, (3) examples
normal complement of chromosomal material
- Inversions
- Reciprocal translocations
- Robertsonian translocations
Unbalanced structural chromosomal abnormalities Definition, (4) examples
abnormal chromosomal content
- Deletions
- Duplications
- Isochromosomes
- Marker (ring) chromosomes
Paracentric inversions___________ the centromere.
exclude
Pericentric inversions___________ the centromere.
include
haploinsufficiency
The contribution of the remaining normal allele is unable to prevent disease
Regarding pericentric inversion, crossover outside the inverted region creates ____ gametes. Crossover inside the inverted region creates 4 gametes with what characteristics?
normal; 1 normal, 2 duplications/deletions (unbalanced), 1 inversion (balanced)
Regarding paracentric inversion, crossover creates 4 gametes with what characteristics?
1 normal, 1 dicentric deletion (non-viable, unbalanced), 1 acentric deletion (non viable, unbalanced), 1 inversion (balanced)
acentric
no centromere (not viable)
dicentric
two centromeres (not viable)
Reciprocal translocations separate in what three ways, and at what stage of mitosis? Which is preferred?
At anaphase, quadrivalent chromosomes separate via alternate, adjacent-1, or adjacent-2 segregation. Alternate is preferred.
Alternate segregation, the most frequent meiotic segregation pattern, produces gametes that have either ________ or _________, both of which are ________ (balanced/unbalanced). Adjacent-1 and adjacent–2 segregation mechanisms lead to ________ (b/u) gametes.
normal chromosome complement; two reciprocal translocation chromosomes; balanced; unbalanced
Chronic Myelogenous Leukemia is caused by what chromosomal structural abnormality?
46,XX,t(9;22)(q34;q11.2). Reciprocal translocation between chromosome 9 and 22, (known as the “Philadelphia chromosome”)
Robertsonian translocation is what? 45,XY,der(14;21)(q10;q10) What is unusual here?
Fusion of two acrocentric chromosomes within their centromeric regions, resulting in the loss of both short arms (containing rDNA repeats). Result in the reduction of chromosome number, but are considered balanced rearrangements because the loss of some rDNA repeats is not deleterious. Often involve chromosome 14.
Ring Chromosome:
a chromosome fragment that circularizes and acquires kinetochore activity for stable transmission to daughter cells (also called a marker chromosome). Sample karyotype: 46,XY,r(13)(p11q34)
Isochromosome:
a chromosome in which one arm is missing and the other duplicated in a mirror-image fashion, possibly occurring through an exchange involving one arm of a chromosome and its homolog at the proximal edge of the arm, adjacent to the centromere.
5 mechanisms that lead to Down’s syndrome
1) meiosis I nondisjunction (maternal) (95%) 47,XY,+21
2) Robertsonian translocation (4%) 46,XX,der(14;21)+21
3) Isochromosome (21q21q translocation) 46,XY,i(21)+21
4) Mosaic Down syndrome (milder, more variable)
5) Partial trisomy 21 (very rare, only a portion of chromosome 21 duplicated)
Cri du chat syndrome
del(5p15.2)
microcephaly
characteristic cry
seizures, intellectual disabilities
Angelman syndrome
del(15q11-q13) (maternal deletion, paternal epigenetic silencing).
seizures
intellectual disabilities
Characterized by weakness of the foot and lower leg muscles, foot deformities known as hammertoes, and weakness and muscle atrophy of the hands late in the course of the diseaseutosomal dominant disorder caused by a duplication of 17p11.2, containing the gene for peripheral myelin protein-22 (PMP-22)
Charcot-Marie-Tooth Disease
DiGeorge syndrome (del 22q11)
defects in the heart absent or hypoplastic thymus and parathyroids, congenital heart disease
Velocardiofacial syndrome (del 22q11)
cleft palate, lateral nasal buildup cardiac septal defects
Prader-Willi syndrome
del(15q11-q13) (paternal deletion, epigenetic maternal silencing) hypotonia, hypopigmentation, hypogenitalism, obesity
Parental imprinting (aka genetic imprinting or gametic imprinting) represents an important epigenetic mechanism of inheritance. How does it work?
Inherit genes in a silenced state from one of the two parents, and in a transcriptionally active state from the other, individual is functionally hemizygous for these genes. Allele-specific methylation of CpG islands, <1% genes affected by this mechanism.
How does Prader-Willi syndrome arise from parental disomy?
maternal gamete is disomic, paternal is normal—->trisomic conceptus (normally inviable)—->nondisjunction leaves 2 maternal chromosome 15—->both are transcriptionally silenced——>Prader Willi
Gene poor chromosomes
13, 18, 21 (viable trisomies)
2 classes of repetitive DNA sequences (aka retrotransposons)
1) Tandem repeats, i.e. “satellite DNAs” 2) Dispersed repetitive elements
Tandem repeats are a class of __________. Give two examples.
Repetitive DNA sequence. 1) Found in heterochromatic regions on chromosome 1, 9, 16 and Y. 2) Alpha-satellite repeats near centromere.
Dispersed repetitive elements are a class of __________. Give 2 examples. Why are they of medical significance?
Repetitive DNA sequence. 1) Alu family (SINE): 300 bp; 500,000 copies in genome 2) L1 or (LINE) family: 6 kB; 100,000 copies in genome. May cause disease by insertion into genes and aberrant recombination.
An SNP is likely to occur how often between 2 people?
1 SNP every 1000 bp
4 categories of genomic DNA, % occupied by each.
Translated/protein-coding sequences (1.5% of genome)
Genes (20-25%)
Single-copy sequences (50%)
Repetitive DNA (40-50%)
How many genes are there (estimate)?
25,000 to 30,000 genes
Name 3 types of genes
protein coding, RNA coding, pseudogenes (with or without introns), (Pseudogenes are nonfunctional)
How many acrocentric chromosomes are there? Which numbers?
There are five acrocentric chromosome pairs, namely 13, 14, 15, 21, and 22.
