Meiosis and Common Chromosomal Anomalies Flashcards by Joel Glotfelty

Fertilization of a female oocyte (gamete) by male spermatocyte (gamete) reconstitutes the 46 chromosome number in the

Zygote (diploid, N = 23)

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How are autosomes and sex chromosomes characterized?

) Size
) Centromere index
) Chromosome G-bright

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What is the centromere index?

Length of p arm / total chromosome length

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Low AT/GC ratio, rich in SINE repeats and Alu sequences, early replicating, contain “housekeeping genes”, not tissue specific, and rich in transcribed genes give

Bright G bands

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Diploid cells replicate and divide into two identical diploid cells

Meiosis I

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DNA cells replicate and the replicated homologous chromosomes establish connections (synapsis)

Prophase I

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Homologous chromosome pairs are ordered in the middle of the cell

Metaphase I

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There is chiasmata at the chromosome ends, and the homologous pairs migrate to opposite poles of the cell

Anaphase I

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The formation of nuclei and two daughter cells

Interkinesis I

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Separates sister chromatids and is made up of Prophase without DNA synthesis, metaphase, and anaphase, and results in 4 haploid cells

Meiosis II

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When there is no separation of homologues between metaphase and anaphase

Non-disjunction Meiosis I

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Non-disjunction in meiosis I will lead to

2 Disomic gametes and 2 monosomic gametes

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When there is no separation of sister chromatids between metaphase and anaphase

Non-disjunction Meiosis II

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Non-disjunction Meiosis II results in two normal gametes and

One disomic gamete and one nullisomic gamete

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In Males, we see meiosis I followed by Meiosis II starting at puberty. Male meiosis allows for the development of

4 spermatids

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In females, meiosis I begins early in intrauterine development and stops before

Birth “diplotene”

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Only 20% of the 6-7 million original oogonia survive as primary oocytes that are arrested in

“Dictyotene” until puberty

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With folliculogenesis, meiosis-I is completed with the extrusion of the 1st polar body at the time of

Ovulation

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Completion of meiosis-II with the extrusion of the 2nd polar body occurs at

Fertilization

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Female meiosis ends with

1 Mature oocyte and 2 lost polar bodies

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Can be used to determine parental origin of chromosomes

Polymorphic CA-repeats

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Polymorphic markers at the beginning of the p-arm or q-arm of the chromosome permits the differentiation of whether non-disjunction occurred in

Meiosis I or Meiosis II

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Non-disjunction in meiosis I will be indicated by markers that are

Heterozygous close to the centromere

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Non-disjunction in meiosis II will be indicated by markers that are

Homozygous close to the centromere

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Chromosomal synapsis is driven by DNA homology resulting in a quadri-radial arrangement with 16 possible segregations of which only

2 are balanced (12%)

Leads to acentric/dicentric chromatids with duplications/deficiencies or genetic information

Recombination in inversion loop during meiosis I

All female are mosaic. A few patients with non-random inactivation of the X chromosome that carry an X-linked disorders or that are Homozygous for the X-chromosome could manifest

X-linked conditions

The random and clonal X-inactivation in females at blastocyst stage for gene dosage compensation with a male

Mary Lyon Hypothesis

Refers to the situation in which 2 copies of a chromosome come from the same parent, instead of 1 copy coming from the mother, and 1 copy coming from the father

Uniparental Disomy

Fertilization with hyperhaploid (disomic) gamete with subsequent loss of the normally inherited chromosome from the other gamete (trisomy rescue) during mitosis causes 1-2% chromosomal mosaicism detected in

Placental samples

Determined by: 1) Degree of mosaicism 2) Genomic imprinting mechanisms in affected chromosomes 3) The non-Mendelian expression of monogenic disorders that map to that chromosome 4) by the combination of all these factors?

Fetal phenotype

Changes in gene expression in response to the environment

Epigenetics

Reversible condensed chromatin conformation represses

Transcription

This regulatory mechanism of gene expression is also clinically relevant for placenta differentiation and function causing Intrauterine fetal growth restriction

Imprinting

Imprinting has been reported on chromosomes

7, 11 (Beckwith Wiedemann), 15 (Prader WIlli/ Angleman), and X (inactivation)

Allow for genetically unique newborns across generations with a 46 chromosome complement.

Sexual reproduction and Meiosis

The consequence of random distribution of homologous chromosomes (8,388,608 possible combinations) together with the formation of Chiasmata among non-sister chromatids during Meiosis with DNA crossing over events

Genetic Diversity

A meiotic non-disjunction even leads to numerical chromosomal abnormalities in the

Zygote

What are two sexual differentiation and sex-chromosome anomalies resulting from non-disjunction events?

1. ) Turner Syndrome (45, X) | 2. ) Klinefelter Syndrome (47, XXY)

Affects 4% of all conceptus. Characterized by cystic hygroma, gonadal dysgenesis, and short stature

Turner Syndrome

Affects 1 in 1,000 males, tall, hypogonadism, | gynecomastia, social dysfunctions. Mental Retardation associated with increasing numbers of X chromosomes in males

Klinefelter syndrome

Affects 1 in 7,500 births with Heart/ CNS/ Renal | abnormalities, growth restriction, Micrognathia, Omphalocele, Equinovarus, Clenched hands

Edwards syndrome (47, XX, +18)

Affects 1 in 20,000 births with IUGR, CL/P, CNS, Renal, | Heart, Omphalocele, Equinovarus, Polydactyly

Patau Syndrome (47, XY, +13)

The most common genetic cause of mental retardation

Down Syndrome (47, XX, +21)

Overexpression and interactions of multiple genes from chromosome 21 cause

Down Syndrome (47, XX, +21)

A translocation resulting in an even exchange of genetic information with no genetic information extra or missing

Balanced translocation

In a newborn, almond-shaped eyes with up slanting palpebral fissures, epicanthal folds, small dysplastic ears, depressed nasal bridge with mid face hypoplasia, strabismus, and brushfield spots suggests

Down syndrome

Brachycephaly, i.e. round head shape w/flattened occiput and excess nuchal skin, hypotonia, atlantoaxial instability, joint laxity, shallow acetabular angle are also indicators of

Down Syndrome

Affects 1 in 15,000 liveborn with morbid obesity, short stature, hypogonadism, mental retardation, and hiyperphagia -Due to a paternal deficiency (deletion) of the 15q11-13 and imprinting of the maternal chromosome

Prader-Willi Syndrome

The affected have severe mental retardation, absent speech jerky gait, protruding tongue, and inappropriate laughter -Due to a maternal deficiency of the 15q11-13 loci (deletion) and imprinting of the paternal chromsome

Angleman Syndrome

No separation of sister chromatids; disjunction of homologues results in segregation of alleles

Meiosis I

There is no S phase in

Meiosis II

Nullisomic gametes yield -Lethal except for X chromosome

Monosomic zygotes

Disomic gametes yield -Lethal except for X, Y, and a few small autosomes (13, 18, 21)

Trisomic Zygotes

Create partial trisomy/monosomy syndromes

Balanced translocations

Imprinting will result in disease if the individual has

Uniparental Disomy (ex: Prader-Willi and Angleman syndromes)

Result from a uniparental disomy of chromosome 15

Prader-Willi and Angleman syndromes

Characterized by chromosomal synapse driven by DNA homology resulting in a quadrivalent arrangement with 16 possible segregations, of which only alternate segregation can lead to 2 balanced gametes (12%)

Balanced translocation

Phenotypically normal parents with pericentric inversion can have children with

deletions/duplications (5-10% risk)

Results in 4 chromosomes coming together in synapses in prophase I

Balanced translocation

All the cells in our body have 46 chromosomes, the purpose of meiosis is to create gametes that only have

In G-banding, the bright bands are the ones rich in

Genes

The most common mutations in humans

Chromosomal abnormalities

What percentage of 1st trimester spontaneous pregnancy losses have chromosomal abnormalities?

50%

If it occurs in the egg, nondisjunction is more common in

Meiosis I

If it occurs in the sperm, non-disjunction is more common in

Meiosis II

In females, meiosis-I begins early in intrauterine development and stops in the 4th stage of prophase I known as

Diplotene

Only 20% of the 6-7 million original oogonia survive as primary oocytes that are arrested in

Dictyotene (part of prophase I)

The polar body from meiosis I with 2 sister chromatids

1st Polar body

The polar body from meiosis II with 1 sister chromatid

2nd Polar body

When one cell line is normal and the other cell line is trisomic

Mosaic form

Phenotypically normal parents with pericentric inversions can have children with

Deletions/duplications

How many Barr bodies are there?

Barr bodies = # X-chromosomes - 1

A disorder that affects males because they do not have an extra X chromosome to compensate

Duchenne Muscular Distrophy

Duchenne muscular dystrophy should not appear in females unless there is a skewing of the

X inactivation centers

When 2 chromosomes are inherited from the same parent -enables AR diseases to appear when only one parent is a carrier

Uniparental Disomy

3% of all down syndrome cases result from parents that have a

Balanced translocation

The robertsonian translocation 45, XX, der(21;21) has a recurrence risk of

100%

The rate of down syndrome identification after 20 weeks of gestation is

1 in 2000

How many americans have down syndrome?

400,000

Free fetal DNA in maternal circulation can also be used for

Aneuploidy screening

Integrates image of fetus with biochemical maternal age

Sequential Integrated Screening Test

Step 1 of the sequential integrated screening test occurs in trimester 1 and step 2 in trimester 2. How efficient is the test for detecting down syndrome?

98%

a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections. The fetal DNA is examined for genetic abnormalities. -The most common reason to have this test is to determine whether a baby has certain genetic disorders or a chromosomal abnormality, such as Down syndrome.

Amniocentesis

A test made in early pregnancy to detect congenital abnormalities in the fetus. -A tiny tissue sample is taken from the villi of the chorion, which forms the fetal part of the placenta.

Chorionic Villous Sampling

What is the frequency for chromosomal abnormalities for: 1. ) Abnormal complement of sex chromosomes 2. ) Autosomal trisomy 3. ) Translocation (mostly balanced) 4. ) Total

1. ) 1/500 2. ) 1/700 3. ) 1/400 4. ) 1/150

What is the procedure related risk for US-guided diagnostic amniocentesis?

1 in 300

A recombination of an inversion creates an

Acentric/dicentric chromosome

Balanced translocations create

Partial monosomy/trisomy syndromes