Podcast Beta
Questions and Answers
What is the expected frequency of phenotypes from a monohybrid cross between true-breeding parents with two different traits?
What is the most probable cause of a different karyotype found only in a growth on a healthy individual with a normal chromosome number?
Which cross would yield a 1:1:1:1 ratio of four phenotypes in offspring?
What are the gametes produced by an individual who is heterozygous for two unlinked traits A and B?
Signup and view all the answers
In a cross between a short purple and a tall white plant yielding all tall purple offspring, what does this imply?
Signup and view all the answers
If an individual with the genotype Aa is crossed with aa, what is the probability of obtaining recessive offspring?
Signup and view all the answers
What type of inheritance pattern is most commonly associated with traits located on the X chromosome?
Signup and view all the answers
What is an example of aneuploidy related to chromosome abnormalities?
Signup and view all the answers
What is the expected phenotypic ratio from a dihybrid cross of Aa x Aa?
Signup and view all the answers
In a test cross involving a recessive sex-linked trait, what is the probability of obtaining affected male offspring when crossing an affected female with an unaffected male?
Signup and view all the answers
Which term describes the process involving changes in gene expression for sex determination?
Signup and view all the answers
What defines the bivalent in meiosis, particularly when there are three chromosomes?
Signup and view all the answers
Which of the following is the most likely cause of a trisomy during meiosis?
Signup and view all the answers
What is the probability of producing carrier females when an unaffected female is crossed with an affected male for a recessive X-linked trait?
Signup and view all the answers
How do meiotic errors differ from mitotic errors?
Signup and view all the answers
What structure is necessary to fully condense a chromosome in its most duplicated form?
Signup and view all the answers
What signifies the transition from euchromatin to heterochromatin?
Signup and view all the answers
What can result from nonallelic recombination of sister chromatids?
Signup and view all the answers
In terms of X-inactivation, what is the first step?
Signup and view all the answers
What is the outcome when maternal imprinting does not occur in a differentially methylated region?
Signup and view all the answers
Which type of inheritance pattern is displayed by mitochondrial genomes?
Signup and view all the answers
What is typically observed when paternal gene deletion occurs in chromosome 15’s differentially methylated region?
Signup and view all the answers
The quadrivalent resolution with the best outcomes typically involves what?
Signup and view all the answers
What effect will rapid demethylation of mono- or dimethylated histones have?
Signup and view all the answers
Which statement accurately describes the gene expression in Angelman syndrome?
Signup and view all the answers
What characterizes pericentric inversions compared to paracentric inversions?
Signup and view all the answers
What are the consequences of uniparental disomy for chromosome 15?
Signup and view all the answers
Between isodisomy and heterodisomy in uniparental disomy, which best describes the origin of alleles?
Signup and view all the answers
Which condition is characterized by developmental and intellectual deficiencies along with epilepsy and tremors?
Signup and view all the answers
What alteration in the banding pattern is indicative of an inversion within chromosomes?
Signup and view all the answers
What is the primary impact of loss of the maternal chromosome 15 in Prader-Willi syndrome?
Signup and view all the answers
How does segmental mosaicism differ from classic mosaicism?
Signup and view all the answers
What characterizes balanced chromosomal rearrangements?
Signup and view all the answers
What best defines deletions in the context of genetic rearrangements?
Signup and view all the answers
Which type of mosaicism involves the presence of two different sets of chromosomes from the same parent?
Signup and view all the answers
What distinguishes isodisomy from heterodisomy in the context of uniparental disomy?
Signup and view all the answers
What is a common consequence of unbalanced chromosomal rearrangements?
Signup and view all the answers
Which form of duplication occurs when a genomic segment is duplicated in the same orientation?
Signup and view all the answers
How does segmental mosaicism differ from classic mosaicism?
Signup and view all the answers
What is typically a detectable outcome of larger chromosomal changes?
Signup and view all the answers
What is the main characteristic of segmental mosaicism?
Signup and view all the answers
Which type of uniparental disomy occurs when both chromosomes are identical?
Signup and view all the answers
What is a potential consequence of uniparental disomy?
Signup and view all the answers
Which of the following best describes heterodisomy?
Signup and view all the answers
Trisomy in a chromosomal profile indicates which of the following?
Signup and view all the answers
Which trisomy is most commonly associated with live births?
Signup and view all the answers
What is the typical survival probability for individuals with Trisomy 18?
Signup and view all the answers
In what scenario is Turner syndrome observed?
Signup and view all the answers
When does nondisjunction most commonly occur during meiosis?
Signup and view all the answers
What distinguishes segmental mosaicism from other forms of mosaicism?
Signup and view all the answers
Which type of chromosome anomaly results from the presence of three copies of a chromosome?
Signup and view all the answers
Which chromosomes are commonly affected in individuals with Turner syndrome?
Signup and view all the answers
In cases of trisomic rescue, what is often the first step?
Signup and view all the answers
Why might there be variable viability among various types of aneuploidies?
Signup and view all the answers
Study Notes
Autosomal Heredity
- Aa x aa yields a 50% probability of recessive offspring
- AA x aa yields a 0% probability of recessive offspring
- A cross between a short purple and a tall white yields all tall purple. If several generations of self-breeding before this experiment never causes this mixed phenotype, this outcome tells you that:
- Tall is dominant to short.
- Purple is dominant to white.
- Both traits are linked in cis.
Autosomal Heredity and Probabilities
- The dihybrid cross is most commonly used to study the independent assortment of two genes.
- The backcross or testcross for a monohybrid would be a cross between the F1 generation and a homozygous recessive individual.
- It is necessary to do the testcross for evaluating independent assortment because it allows you to determine the genotype of the F1 generation.
- If a gene is linked in trans, we expect the progeny to inherit the dominant or recessive alleles together.
Sex-linked Heredity
- An affected female crossed with an unaffected male for a recessive sex-linked trait has a 50% probability of affected male offspring.
- An unaffected female crossed with an affected male for a dominant X-linked trait would have a 50% chance of affected males.
- An unaffected female crossed with an affected male for a recessive X-linked trait would have a 50% probability of producing carrier females.
Sex Determination
- All sex determination can be thought of as epigenetic because it involves changes in gene expression.
- Sex determination that involves changes in conditions such as temperature is environmental sex determination.
- Changes in the ratio of males to females expected can be caused by environmental factors like pollution, chemicals, or temperature.
- Heterogametic sexes are those with two different sex chromosomes (e.g., XY in humans) and likely have genes for which they are hemizygous.
Meiosis and Recombination
- The order of meiotic prophase I is: leptotene, zygotene, pachytene, diplotene, diakinesis.
- At the diplotene stage, chromosomes would exhibit the most force pushing them apart.
- Homologous recombination occurs during the pachytene stage. The synaptonemal complex enables non-homologous chromosomes to align and exchange material.
- Crossing-over begins during the pachytene stage of meiosis I.
- The bivalent refers to paired homologous chromosomes, and if there are 3 chromosomes (a trisomy), a trivalent is formed.
Meiosis
- Meiotic errors are different from mitotic ones because they can result in aneuploidy (abnormal number of chromosomes), which is not possible in mitosis.
- Proper segregation in meiosis I involves the separation of homologous chromosomes.
- The two factors that lead to increased diversity in offspring are:
- Independent assortment of chromosomes
- Crossing over.
Mitosis and Errors in Segregation
- The most likely cause of a trisomy during meiosis is a nondisjunction event, where chromosomes fail to separate properly.
- A mitotic error that generates mosaicism found ONLY in the placenta is known as confined placental mosaicism.
- Two issues with mosaicism in terms of human testing, especially prenatally, are:
- It is not always possible to determine the extent of mosaicism.
- It is not always possible to predict the phenotypic effects of mosaicism.
Aneuploidies
- The only viable whole chromosome monosomy is 45,X (Turner syndrome).
- The most likely cause of early pregnancy loss is aneuploidy.
- Trisomy is worse than monosomy in terms of autosomes because it results in a greater imbalance of gene expression.
- There is a phenotype associated with 47,XXY (Klinefelter syndrome) because the extra X chromosome disrupts the normal balance of gene expression.
Chromosome Structures
- Incorporation of CENP-A into the nucleosome promotes the formation of a centromere.
- NORs (Nucleolar Organizing Regions) are located on the satellite regions of acrocentric chromosomes. They contain genes for ribosomal RNA.
- In the most condensed form for duplicated chromosomes, cohesin is needed to fully condense the chromosome, while condensin holds sister chromatids together.
- TTAGGG repeats in humans are most likely to be found at telomeres, which are protective caps at the ends of chromosomes.
Chromosome Structures
- When the sequence of TTAGGG in humans gets critically short, the cell is likely to enter senescence.
- Lengthening or maintenance of telomeres should only occur in germ cells, stem cells, and some immune cells to ensure that they have the potential for continued division.
Karyotyping
- Normal Male: 46,XY
- Normal Female: 46,XX
- Trisomy of chromosome 21: 47,XX+21 or 47,XY+21
- Karyotype of only known viable nonmosaic whole chromosome monosomy: 45,X (Turner Syndrome)
- Klinefelter Syndrome: 47,XXY
Chromatin
- Histone deacetylase activity would be expected if transitioning from euchromatin to heterochromatin. Deacetylation of histones makes DNA less accessible, facilitating the formation of heterochromatin.
- Chromatin remodeling using the Chromatin Remodeling Complex can reposition nucleosomes to regulate gene expression.
- The addition of methyl groups is correlated with the repression of gene expression.
- Histone 3 (H3) is expected to be trimethylated when the corresponding nucleosome is located within a region that is organized as heterochromatin.
- Rapid demethylation of mono- or dimethylated histones would cause activation of gene expression.
Structural Rearrangements
- Nonallelic recombination of sister chromatids would cause gene duplication and deletion.
- The larger the structural rearrangement in inversions and translocations, the more likely it is to be deleterious.
- Interchromosomal exchanges occur between non-homologous chromosomes.
- Allelic exchanges within the inversion loop of a paracentric inversion cause a deletion of genetic material.
- The centromere is expected within an inversion loop when the inversion is pericentric.
- The quadrivalent resolution with the best outcomes is alternate segregation, and it yields two normal chromosomes and two chromosomes with inversions.
- Homologous centromeres will be found together under the alternate segregation pattern.
Imprinting
- If maternal imprinting of a differentially methylated region does NOT happen, we would expect the paternally inherited allele to be active.
- Oogenesis ensures that only a maternal imprinting pattern is inherited by suppressing the paternal imprints during the process of oocyte development.
Prader-Willi and Angelman
- Maternal imprinting shuts off the UBE3A gene in the maternal allele of chromosome 15.
- A paternal gene deletion would cause Prader-Willi syndrome if the gene loss is of chromosome 15’s differentially methylated region.
- In addition to gene deletion, uniparental disomy (inheritance of both copies of a chromosome from one parent) can also cause the manifestation of the diseases associated with chromosome 15 anomalies.
X-inactivation
- The first step of X-inactivation is the recruitment of the XIST gene, which is transcribed into a long non-coding RNA that coats the inactive X chromosome.
- The second step of X-inactivation is the silencing of genes on the inactive X chromosome.
- PAR1 and PAR2 are pseudoautosomal regions on the X and Y chromosomes, they escape X inactivation and are expressed from both the active and inactive X chromosome.
Non-mendelian Inheritance
- Mitochondrial genomes are replicated independently of the nuclear genome.
- Human mitochondria are inherited maternally.
- The presence of paternal mitochondria when maternal inheritance is expected is termed heteroplasmy.
A Review of Block 2
- Remember, inheritance questions can be simplified by using Punnett squares.
- If you get stuck, go back to the basics and change the terms to letters.
- If there is a blank, then the question is leaning closer to a DEFINE objective.
- If the question is shorter, it is meant to be a quick one that is based on a fact rather than something that should take a long time to work through.
Basic Genetics
- There are 46 human chromosomes, 22 pairs of autosomes and one pair of sex chromosomes.
- A mosaic individual has two or more different cell lines with different karyotypes.
- A chimera individual has cells derived from two or more different zygotes.
- The most probable cause of this different karyotype is a mitotic error, such as nondisjunction.
Making Gametes
- The genotype of an individual who is heterozygous for two unlinked traits A and B is AaBb. Their possible gametes are AB, Ab, aB, ab.
- The most probable gametes from an individual with the genotype AaBb linked in cis are AB and ab.
- Gametes that represent recombinant gametes from an individual who is heterozygous for genes linked in trans are Ab and aB.
Chromosomes and Meiosis
- Chromosomes consist of linear sequences of genes which determine the physical expression of a phenotypic trait.
- Multiple stages of chromosome condensation occur in Prophase I of meiosis: Leptotene, Zygotene, Pachytene, Diplotene, and Diakinesis.
- Homologous chromosomes are independent and can produce over 8.3 million unique combinations of chromosomes.
- Premature separation of chromosomes is a major cause of aneuploidy.
- Recombination between linked genes involves homologous crossing over, where alleles are exchanged between homologous chromosomes.
- Recombination creates recombinant chromosomes, which have different combinations of alleles than the parental chromosomes.
- In a double heterozygote, cis configuration means mutant alleles are on the same chromosome, while trans configuration means mutant alleles are on different homologues.
- Homologous recombination repair uses similar mechanisms to traditional homologous recombination, such as homology search and strand invasion.
- Inappropriate alignment during recombination can result in duplications and deletions.
- Chromosome deletions are a common genetic abnormality.
Cytogenetics and Chromosomes
- The human karyotype consists of 22 pairs of autosomes and one pair of sex chromosomes.
- Key features of a chromosome include: telomere, centromere, kinetochore, heterochromatin, and euchromatin.
- FISH and microarray analysis are used for chromosome analysis.
- The centromere's location determines a chromosome's shape:
- Metacentric: middle of chromosome
- Submetacentric: closer to one end
- Acrocentric: near one end
- Telocentric: at the telomere
- Centromeres contain repetitive DNA and histone variants, including CENP-A, which is found exclusively at functional centromeres.
- Neocentromeres form when centromeric histones inappropriately incorporate into non-centromeric regions.
Kinetochore
- The kinetochore is a conserved structure involved in microtubule attachment.
- It contains regulatory components, including kinases and phosphatases, that play a critical role in microtubule attachment and regulation.
- Aurora B kinase and cyclin-dependent kinase 1 (CDK1) are crucial for kinetochore function.
Telomeres and Telomerase
- Telomeres protect chromosome ends through capping.
- Short telomeres can lead to reduced chromosome integrity, cellular senescence, and trigger DNA repair mechanisms in G1 phase.
- Telomerase maintains telomere length in stem cells but should not be active in normal somatic cells.
- Telomerase consists of two components: hTERT and hTR.
Nucleolar Organizer Regions (NORs)
- NORs are located on the satellite stalks of acrocentric chromosomes.
- They play a critical role in nucleoli formation during interphase.
- NORs contain ribosomal RNA genes and are involved in rRNA production.
Aneuploidy
- Trisomy: Three copies of a chromosome
- Monosomy: One copy of a chromosome
- Trisomy for all autosomes has been reported in spontaneous pregnancy losses, with varying frequencies.
- Monosomies are extremely rare in both spontaneous losses and live births, suggesting lethality before sufficient tissue development.
- Turner Syndrome (45,X) is the sole exception for adult viability in monosomy.
Mechanisms of Meiosis I Nondisjunction and Mitotic Nondisjunction
- Meiosis I nondisjunction occurs when homologous chromosomes fail to separate properly during meiosis I.
- Both chromosomes can migrate to one pole, or premature separation can occur.
- Mitotic nondisjunction occurs when sister chromatids fail to separate properly during mitosis, resulting in daughter cells with uneven genetic content.
Timing and Consequences of Mitotic Nondisjunction
- Mitotic nondisjunction can lead to varied outcomes depending on the timing and cell type affected.
- Mosaicism is possible, with different cell populations having different genetic compositions.
- Confined placental mosaicism (CPM) and fetal mosaicism can occur.
Uniparental Disomy (UPD)
- UPD occurs when both copies of a chromosome or chromosome region are derived from a single parent instead of one copy from each parent.
- Most UPD cases have no phenotypic consequences but can have implications for differentially methylated regions and autosomal recessive gene homozygosity.
- UPD can be either isodisomy (both chromosomes are identical) or heterodisomy (both chromosomes are different).
- Mechanisms of UPD include:
- Gametic complementation
- Trisomic rescue
- Mitotic error and rescue
Chromosome Rearrangements
- Nonallelic recombination due to regions of homology can lead to chromosome rearrangements.
- Low copy repeats are frequently involved, while high copy repeats can also contribute.
- Examples include Alu-mediated recombination and α-satellite recombination.
Types of Recombination
- Recombination can be interchromosomal (across homologs) or intrachromosomal (within or between sister chromatids).
- Normal recombination occurs at the same loci or alleles on homologous chromosomes or sister chromatids.
Balanced vs. Unbalanced Rearrangements
- Balanced rearrangements involve no net loss or gain of genetic information.
- They are generally phenotypically normal, although positional effects may cause observable phenotypes.
- Unbalanced rearrangements involve additional or missing genetic material, leading to clinical consequences.
- Molecular cytogenetic techniques are crucial for detecting chromosome rearrangements.
Categories of Structural Rearrangements
- Deletions (partial aneuploidies), Duplications, Inversions, Translocations
Deletions
- Deletions are losses of genetic material, also known as partial aneuploidies, segmental aneusomies, or contiguous gene disorders.
- Deletions can affect adjacent material.
- Small deletions can follow Mendelian inheritance, while most are de novo.
- Expressivity and penetrance are important considerations for deletions.
- Gonadal mosaicism in parents and dynamic mosaicism from postzygotic mitoses are possible.
Duplications
- Duplications are extra copies of a genomic segment, causing partial trisomy.
- Pure duplications have no other imbalances, while combination with other rearrangements is also possible.
- Tandem duplications involve a contiguous doubling of a segment:
- Direct: Same orientation as original segment, most common in humans.
- Inverted: Opposite orientation.
- Duplication phenotypes are generally less severe than deletion phenotypes.
Inversions
- Inversions are intrachromosomal rearrangements where a segment is reversed.
- Breakpoints occur at two locations on the same chromosome.
- Two types:
- Pericentric: Breakpoints on either side of the centromere, affecting arm ratio.
- Paracentric: Breakpoints on the same side of the centromere, affecting only one arm.
- Presence is indicated by altered banding pattern.
Crossing Over in Inversions
- Crossing over in inversions can create chromosomal loops.
- This can lead to deletions, duplications, or other chromosomal abnormalities.
Disease Examples: Prader-Willi vs. Angelman Syndrome
- Both Prader-Willi and Angelman syndromes are caused by deletions or UPD in the 15q11-13 region.
- The phenotypic consequences depend on whether the maternal or paternal copy of the region is affected.
- Prader-Willi: Loss of paternal copy, leading to hypotonia, obesity, and hypogonadism.
- Angelman: Loss of maternal copy, leading to developmental and intellectual deficiencies, epilepsy, and tremors.
Translocations
- Translocations are interchromosomal rearrangements where material is exchanged between nonhomologous chromosomes.
- Can be reciprocal (exchange of material between two chromosomes) or Robertsonian (fusion of two acrocentric chromosomes).
- Balanced translocations are generally phenotypically normal, while unbalanced translocations can cause significant problems.
Common Examples of Human Chromosome Rearrangements
-
Inversions:
- _Inversion 9:** A common inversion that may result in a slight risk of infertility or birth defects.
-
Deletions:
- Cri-du-chat syndrome (5p-): Characterized by severe intellectual disability, a distinctive cat-like cry, and other physical abnormalities.
- Wolf-Hirschhorn syndrome (4p-): A syndrome with a wide range of symptoms, including intellectual disability, facial dysmorphic features, and seizures.
-
Duplications:
- Duplication 15q 11.2-13: A common duplication contributing to Angelman syndrome.
-
Translocations:
- Philadelphia chromosome (t(9;22)): Associated with Chronic Myeloid Leukemia (CML).
- Robertsonian translocation (t(13;14), t(14;21) or t(15;21): Can lead to recurrent miscarriages or the birth of infants with genetic disorders.
Applications of Cytogenetics
- Paternity testing: Identifying the father of a child.
- Prenatal diagnosis: Screening for chromosomal abnormalities in a fetus before birth.
- Cancer diagnosis and prognosis: Identifying chromosomal abnormalities that can indicate the presence of cancer or predict its course.
- Human evolution: Studying chromosomal rearrangements that have occurred over time to help understand the evolution of the human genome
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
