Genetics - Week 1 And 2

Front 1

When do human primordial germ cells differentiate into ovaries and testes?

Back 1

After the 6th week of development.

Front 2

When are spermatogonia?

Back 2

A stem cell line that lines the seminiferous tubules and divides meiotically to give rise to sperm. Develop from primordial germ cells and continue to divide mitotically to replace themselves throughout lifetime.

Front 3

Male Meiosis I

Back 3

diploid primary spermatocytes give rise to 2 secondary spermatocytes.

Front 4

Stages of spermatogenesis

Back 4

1spermatogonium --> 1diploid primary spermatocyte --> 2haploid secondary spermatocyte --> 4haploid spermatids --> 4 sperm(differentiation without division)

Front 5

Which germ cell lines (males or females) undergo mitosis during lifespan?

Back 5

Males only. Female germ cell lines only undergo meiosis, as all development of primary oocytes is complete by birth.

Front 6

When does female meiosis II begin? when is it completed?

Back 6

Female meiosis II begins upon ovulation, halts at metaphase prior to fertilization, and is completed after fertilization.

Front 7

How many eggs and polar bodies are produced from one primary oocyte?

Back 7

one haploid ovum and 2 polar bodies. (The first polar body is extruded at completion of Meiosis I, second after completion of Meiosis II)

Front 8

At what stage do primary oocytes arrest before puberty?

Back 8

Prophase I

Front 9

How many oocytes will mature before birth?

Back 9

400

Front 10

Where and when does fertilization cccur normally?

Back 10

In the fallopian tube one day after ovulation.

Front 11

What genetic/cellular defects can you 100% blame on your mother?

Back 11

mitochondrial defects

Front 12

What is haploinsufficiency? Name examples.

Back 12

50% of normal gene product is not enough to give a normal phenotype. example: familial hypercholesterolemia

Front 13

What is a dominant negative mutation? Name examples.

Back 13

gene product is part of a multisubunit complex and one bad subunit destroys the whole complex. Example: p53 mutations in cancer. Heterozygotes end up with less than 50% WT activity.(one bad apple really does destroy the bunch)

Front 14

What is a gain of function mutation? example?

Back 14

mutant gene product has function/activity different from WT. Only one specific or mutations in one small region of the gene cause disorder. Example: mutation that knocks out allosteric inhibitor binding site on an enzyme.

Front 15

What are the molecular reasons for dominant inheritance?

Back 15

1)haploinsufficiency
2)dominant negative
3)gain of function

Front 16

Rules of pedigrees of autosomal dominance.

Back 16

1) affected people in all generations
2)both males and females equally affected
3)most common marriage type seen = D/d X d/d --> half affected (D/d), half unaffected (d/d)
*D/D can be lethal in some diseases, and frequently more severely affected than D/d

Front 17

Occurrence of new mutations

Back 17

easy to know for dominant disorders
achondroplasia high in new mutations (80%)
Huntingtons very rare - almost always have affected parent

Front 18

Cause of Achondroplasia

Back 18

mutation in FGFR3 one isoform of fibroblast growth factor receptor. Almost always gly380arg substitution. (lethal in homozygous state)

Front 19

Characterisitcs/rules for autosomal recessive inheritance

Back 19

1)equal number of affected males and females
2)typically unaffected, carrier parents
3)sporadic occurrence, skipped generations
4)risk of affected child is 1/4 for 2 carrier parents per conception (most commonly seen case)
5)increased risk with consanguinous marriages

Front 20

Compound heterozygotes

Back 20

two different mutations in the two alleles. Phenotype varies according to severity of the combination of mutations. example: beta-thalassemia.

Front 21

What is the probability of carrier status of a phenotypically normal sibling of an individual affected with and autosomal recessive disease?

Back 21

2/3

Front 22

Hemophilia A

Back 22

X-linked recessive disorder characterized by excessive bleeding and inability to clot. caused by mutations in gene for clotting factor VIII, which is located on Xq. Allelic heterogeneity, hundreds of different mutations found.

Front 23

X-linked dominant inheritance

Back 23

affected father X unaffected mother = all daughters and no sons affected
unaffected father X affected mother = 50% of both sons and daughters affected
disease present in all generations.
example: defective tooth enamel.

Front 24

What is locus heterogeneity? What are some examples?

Back 24

The same disorder can be caused by mutations in several genes. examples:
1)Retinitis Pigmentosa
2)autosomal dominant polycystic kidney disease (PKD1 and PKD2)
3)albinism (tyrosinase and P gene)
4)Autosomal recessive deafness

Front 25

Allelic heterogeneity

Back 25

same disease caused by mutations in the same gene. almost all loss of function disorders.
examples: hemophilia A and male cystic fibrosis.

Front 26

Genetic imprinting

Back 26

only either the paternal allele or the maternal allele of a particualr gene is active. examples: prader willi and Angelmann's syndromes.

Front 27

Direct Determination of Recombination Frequency

Back 27

total frequency of non recombinant gametes: 1-theta
total frequency of recombinant gametes: theta
theta ranges from 0 to .5

Front 28

RFLPs restriction fragment length polymorphism

Back 28

specific restriction site that is present on some copies of a chromosome and not on other variants. detected by PCR +restriction digestion or resitrction digestion + southern blotting.

Front 29

minisatellites

Back 29

Variable number of tandem repeats at specific chromosomal site. unit is 20-70bp. detected by restriction digestioin + southern blotting

Front 30

microsatellites

Back 30

highly polymorphic simple short repeats. dinucleotide, tri or tetranucleotide units. number of units varies. detected by PCR.

Front 31

SNPs single nucleotide polymorphisms

Back 31

polymorphic variation in one base pair. detected by sequence analysis or allele-specific probes.

Front 32

What is the Giemsa stain and how is it used?

Back 32

The Giemsa stain is used to observe karyotypes, especially with specific banding (if used with trypsinization). light bands are gene-rick while dark bands are gene poor.

Front 33

Which chromosomes are acrocentric? What is the function of the constricted/stalk region and of the satellite at the end of the p arm?

Back 33

13,14,15,21,22. The stalk/constricted region of p arm encodes 18S and 28S rRNA while the satellite at the end is heterochromatic/non-coding.

Front 34

What is Fluorescence In Situ Hybridization and how is it used?

Back 34

Hybridizes fluorescence tagged probes to chromosomes in various colors. counterstained with dull red propidium iodide. used to detect specific chromosomes, translocations, abnormalities, presence of genes, etc. If entire spectrum of chromosomes is probed, its called spectral karyotyping or SKY. probes can be entire chromosome paint, satellide DNA probes, or locus-specific probes.

Front 35

What are the stats on chromosomal anomalies and/or associated spontaneous abortion?

Back 35

-1% chrom. anomalies at birth
-15% spontaneous abortion, usually 1st trimester
-half of those are due to chrom. anomalies.
-which means chromosomal anomalies are in 8.5% of all recognized pregnancies

Front 36

What are the clinical indications for chromosomal analysis?

Back 36

1) pregnancy in woman 35 years or older
2)family history
3)fertility problems
4)children with problems of early growth and development
5)stillbirth or neonatal death
6)cancer

Front 37

What are the causes of triploidy and tetraploidy?

Back 37

1)Triploid is usually caused by dispermy
2)Tetraploidy is a failure of cytokinesis in post-fertiliztion mitosis.
3)triploid fetuses can sometimes be born alive and survive for a short time after birth, but tetraploids are always spontaneously aborted.

Front 38

What is ploidy level vs. somal level?

Back 38

ploidy = the number of sets of chromosomes, whereas somic level is the number of an individual chromosome.

Front 39

NDJ in which meiosis level produces no normal gametes? NDJ in whcih meiosis level produces 2 normal and 2 abnormal gametes?

Back 39

NDJ M1 produces 2 disomic and 2 asomic gametes, while NDJ M2 produces 2 normal, one disomic (homo) and one asomic gamete.

Front 40

What causes mosaicism in somic level?

Back 40

NDJ in mitosis after fertilization. have some normal cells and some abnormal (trisomic).
these can have variable phenotype.

Front 41

What are the important feature os down syndrome?

Back 41

1)early alzheimer's
2)congenital heart defects
3)recurrence risk with another pregnancy = 1%
4)robertsonian translocation just as severely affected, but mosaics vary in phenotype
5)increased risk with incresing maternal age, especialy 35 or over
6)incidence is 1/800 in general population
7)mental retardation always, typically moderate.
8)many cases prenatally detected by CAmaternal serum screening program

Front 42

What are the characteristics and prognosis of trisomies 18 and 13?

Back 42

1) severe developmental and mental retardation AND poor survival
2)increased incidence with maternal age
3) many cases detected prenatally

Front 43

What causes Cri du Chat syndrome and what are its characteristics?

Back 43

!) caused by deletion on 5p and haploinsufficiency
2)severe mental retardation and neonatal cat-like cry
3)frequently live to be adults

Front 44

What is the cause and characteristics of Prader Willi syndrome?

Back 44

1)microdeletion of 15q11-q132)2)paternal gene imprinting
3)symptoms: hypogonadism, small hands and feet, mental retardation, obesity, short stature, complusive over-eating.
4)70% microdeletion, 30% uniparental disomy

Front 45

What is the cause and characteristics of Angelmann syndrome?

Back 45

1)microdeletion of 15q11-q13, E6 AP gene, which encodes ubiquitin protein ligase
2)maternal gene imprinting
3)symptoms: severe mental retardation, abnormal gait, unusual laugh, seizures, (happy puppet).
4)70% microdeletion, 3-5% uniparental disomy

Front 46

What forms during meiosis 1 in a balanced carrier of robertsonian translocation?

Back 46

a trivalent

Front 47

What's the risk of a balanced carrier of a robertsonian translocation having a child with down syndrome?

Back 47

1)15% per pregnancy of a female carrier
2)5% in a male carrier per pregnancy of his spouse.

Front 48

Can balanced translocation be associated with an abnormal phenotype?

Back 48

Yes, if an essential gene is broken into two pieces.

Front 49

What forms during meiosis 1 in a carrier of a reciprocal translocation?

Back 49

a quadrivalent

Front 50

How is sex determined by the Y chromosome?

Back 50

1)The Y chromosome must be present for gondads to become testes
2)in its absence, gonads become ovaries
3)the SRY gene on the Y chromosome is essential in determining male sex
4)several other genes are required for spermatogenesis such as the AZF a,b,c genes.
5)Large block of heterochromatic DNA in distal region, variable in size.
6)Y is gene poor, about 50 active genes, some homologous to X, some unique.

Front 51

X inactivation and barr body formation in females

Back 51

1) number = number of X-1
2)initiated by XIC (X inactivation Center) on Xq13.
3)caused by transcription of XIST gene, XIST RNA associates with chromosome and inactivates most but not all genes.
4)inactivation is stable, remains through all subsequent mitoses
5)all normal females are mosaics, different X inactive in each cell.

Front 52

What is the genotype and phenotype of Turner's syndrome?

Back 52

1) genotyoes: 45,X; 46,X,i(Xq); 46,X,Xp-; 46,X,Xq-; 45,X/46,XX; 45,X/46,i(Xq); other mosaics
2)all patients --> gonadal dysgenesis and streak gonads; amenorrhea; minimal breast development; sparse or missing pubic hair.
3)Xp- or i(Xq): also short stature and congenital malformations
4)Xq-: gonadal dysgenesis but may have normal stature.
5)structurally abnormal X is always inactivated in all cells.
6)50% 45X

Front 53

What is the genotype and phenotype of Kleinfelter's syndrome?

Back 53

1)tall stature, long limbs, relatively small genitalia, gynecomastia in many, infertility, no germ cells upon testicular biopsy
2)47XXY

Front 54

What is the phenotype of 47XYY?

Back 54

1)Tall male, fertile, mean intelligence decreased, behavior problems
2)caused by NDJ in male meiosis 2

Front 55

What is the phenotype of 47XXX?

Back 55

female, usually tall, fertile,some have learning disabilities and/or behavioral problems, but others are normal in cognitive ability and behavior.

Front 56

Which disorders are caused by abnormal recombination of male X and Y in germline cells? what are the phenotypes?

Back 56

1)46XY FEMALE: SRY deleted, phenotype similar to turner's.
2)46XX MALE: SRY added, on short arm of one X, infertile male.