MBG 3050 Final Exam

What occurs during fertilization?

Gametes fuse, activating the egg to form a zygote, involving species-specific interactions of proteins and receptors.

What is the first stage of early embryo development after fertilization?

The zygote undergoes cleavage, partitioning into smaller cells called blastomeres.

What key structures are formed in the blastocyst?

The blastocyst includes the trophoblast (forms fetal portion of placenta), inner cell mass (ICM, gives rise to embryo), and blastocoel (fluid-filled cavity).

What happens to the inner cell mass (ICM) around day 3 of development?

The ICM undergoes compaction and further development.

What is the process of hatching in embryonic development?

The blastocyst hatches from the zona pellucida (ZP) before implantation.

Where does the blastocyst implant?

The blastocyst implants into the endometrium of the uterus.

What does the trophoblast develop into?

The trophoblast establishes the chorion, the fetal portion of the placenta.

What structures does the inner cell mass (ICM) give rise to?

The ICM gives rise to the epiblast (embryo proper) and the hypoblast (yolk sac).

What are the three embryonic germ layers formed during gastrulation?

Endoderm, mesoderm, and ectoderm.

What is the significance of the germ layers in development?

Each germ layer gives rise to unique differentiated cells and organ systems.

What is monozygotic twinning?

Monozygotic twinning occurs when a developing embryo splits early, resulting in two genetically identical individuals.

What role do Receptor Tyrosine Kinases (RTKs) play in cellular processes?

RTKs are cell surface receptors crucial for cell signaling, including proliferation and differentiation.

How can mutations in RTK signaling pathways lead to disease?

Mutations can cause loss-of-function or gain-of-function, leading to aberrant signaling responsible for diseases like cancer.

What is an example of a gain-of-function mutation in RTK?

Achondroplasia is often caused by gain-of-function mutations in FGFR3, leading to premature activation of the pathway that stops chondrocyte division.

What is the effect of mutations in FGFR2?

Most mutations in FGFR2 cause craniosynostosis.

What disorders are associated with haploinsufficiency mutations in c-Kit or MITF?

Piebaldism and some forms of Waardenburg syndrome.

What is the consequence of homozygous mutations in the Kit signaling pathway?

They result in a more severe phenotype affecting neural crest cell derivatives.

How does aberrant RTK signaling contribute to cancer?

It can drive tumorigenesis, with mutations in pathways like Ras-ERK leading to uncontrolled cell division.

What is the Bcr-Abl fusion protein and its significance?

It is an overactive kinase that constitutively activates downstream signaling pathways, leading to chronic myelogenous leukemia (CML).

What is the role of transcription factors in cellular processes?

Transcription factors bind to DNA to regulate gene expression and mediate cellular responses to external signals.

What are Hox genes and their role in embryonic development?

Hox genes encode transcription factors crucial for patterning the embryo and determining the developmental fate of regions where they are expressed.

How does the order of Hox genes relate to their function?

The order of Hox genes in the cluster parallels their expression along the anterior-posterior axis.

What is the function of MITF in development?

MITF is a transcription factor involved in the Kit signalling pathway, required in neural crest cell derivatives, affecting pigmentation.

What role do Gli transcription factors play in embryonic development?

Gli transcription factors are downstream components of the Sonic hedgehog (Shh) signalling pathway, critical for embryo pattern formation, limb development, and neural differentiation.

What determines gene expression in the presence of Gli transcription factors?

The presence of Gli activator or repressor, coupled with the Shh signal, determines which genes are expressed.

What syndrome is associated with mutations in Gli3?

Mutations in Gli3 can cause Greig syndrome.

What is the role of the p53 gene in cellular processes?

p53 is a tumour suppressor gene that encodes a transcription factor important for cell cycle arrest, induction of senescence and apoptosis, and activation of DNA repair enzymes.

How is sex determined genetically?

Sex is determined by the presence or absence of the Y chromosome.

What is the function of the SRY gene?

The SRY gene on the Y chromosome is the major sex-determining locus that encodes the TDF (testis-determining factor) protein, instructing the primordial gonad to develop into testes.

What is the difference between primary and secondary sex determination?

Primary sex determination involves the development of gonads, while secondary sex determination involves the development of external genitalia instructed by hormones.

Which genes are involved in testicular development?

SRY and Sox9 promote testicular development, while Dax1 may suppress it.

What are intersex conditions?

Intersex conditions involve the presence of both male and female traits in the same individual.

What causes male pseudohermaphroditism?

It can be caused by deletion of SRY, loss of function mutations in SRY or its interacting factors, mutations in the testosterone receptor, mutations in Anti-Müllerian factor, or duplication of DAX1.

What is androgen insensitivity syndrome?

Individuals with androgen insensitivity have a 46,XY karyotype but a female phenotype due to mutations in the testosterone receptor.

What causes female pseudohermaphroditism?

It can be caused by gain of SRY, congenital adrenal hyperplasia (over-production of testosterone), or other genetic factors.

What is true hermaphroditism and its causes?

True hermaphroditism can be caused by translocation of the Y chromosome to the X chromosome or chimerism of XX and XY zygotes.

What are the characteristics of stem cells?

Stem cells can divide to produce specialized cell types and more stem cells (self-renewal) and are capable of extensive proliferation.

How does stem cell potency change during development?

Stem cells exhibit a gradual restriction in potency during development.

What are pluripotent stem cells?

Pluripotent stem cells can differentiate into all cell types of the adult organism, including germ cells, and include embryonic stem (ES) cells and induced pluripotent stem (iPS) cells.

What are multipotent stem cells?

Multipotent stem cells can differentiate into a limited range of cell types within a particular lineage, such as hematopoietic stem cells and epidermal stem cells.

What are totipotent stem cells?

Totipotent stem cells have the highest potency and can give rise to all cell types, including the placenta; the zygote and early embryo cells are considered totipotent.

What is nuclear reprogramming?

Altering nuclear gene expression to change the differentiation state of a cell.

What is somatic cell nuclear transfer (SCNT)?

The process of transferring the nucleus of a somatic cell into an enucleated egg cell, used for reproductive or therapeutic cloning.

What are induced pluripotency (iPS) cells?

Somatic cells reprogrammed to a pluripotent state by introducing specific transcription factors like Oct3/4, Sox2, Klf2, and c-Myc.

How can transcription factors be delivered to induce pluripotency?

Using viral vectors (retroviruses, lentiviruses) or non-integrating methods (plasmids, recombinant proteins).

What is transdifferentiation?

The process of converting one differentiated cell type directly into another using specific transcription factors.

What is gene augmentation/addition in gene therapy?

Adding a normal copy of a gene to cells that have defective copies.

What does elimination of pathogenic mutations involve?

Correcting or repairing mutant alleles using targeted genome editing tools like CRISPR-Cas9.

What is targeted inhibition of gene expression?

Blocking the expression of a mutant allele at the level of transcription, translation, or protein function.

What is targeted killing of specific cells in gene therapy?

Introducing a toxin gene or prodrug-metabolizing gene into diseased cells to make them vulnerable to a drug.

What is indirect killing of diseased cells?

Modifying cells, such as T cells in CAR-T therapy, to recognize and destroy diseased cells.

What are the two methods of modifying cells for gene therapy?

In vivo (directly in the patient's body) and ex vivo (outside the body and then transplanted back).

Why are viral vectors commonly used in gene therapy?

Due to their efficiency in infecting cells and integrating or expressing their genetic material.

What are gamma-retroviruses?

Viral vectors that integrate into the genome, target dividing cells, and have long-lasting transgene expression.

What are lentiviruses and their advantages?

HIV-based vectors that integrate into the genome, target both dividing and non-dividing cells, and have high-level expression with low oncogene activation risk.

What are adenoviruses?

Viral vectors that do not typically integrate, target both dividing and non-dividing cells, and provide transient but high-level expression.

What are adeno-associated viruses (AAVs)?

Vectors that mostly remain episomal, target dividing and non-dividing cells, and have high-level expression with less immunogenicity.

What are liposomes in gene therapy?

Non-viral vectors that are easy to produce and safe but have inefficient DNA transfer and transient gene expression.

What are the hallmarks of cancer?

Self-sufficiency in growth, insensitivity to anti-growth signals, evasion of cell death, limitless replicative potential, sustained angiogenesis, and tissue invasion/metastasis.

What are oncogenes?

Genes that stimulate cell growth and division; activation of one allele can promote cancer.

What are tumor suppressor genes (TSGs)?

Genes that inhibit cell division; generally, both alleles must be inactivated to lose their function.

What is the role of p53 in cancer?

It is a tumor suppressor gene that, when lost, allows evasion of apoptosis signals.

What is the significance of telomerase in cancer?

It provides limitless replicative potential by maintaining telomere length.

What are the two main roles of tumor suppressor genes (TSGs)?

TSGs can act as gatekeepers, regulating the cell cycle or causing growth inhibition (e.g., RB, APC), or as caretakers, repairing DNA damage and maintaining genome integrity (e.g., p53, BRCA1/2).

What is loss of heterozygosity (LOH)?

LOH occurs when a somatic cell has only one functional copy of a gene due to the loss or inactivation of the other allele, which is particularly relevant for tumor suppressor genes.

How does Knudson's 'two-hit' hypothesis relate to cancer development?

The hypothesis suggests that an individual may inherit one mutated allele of a tumor suppressor gene, and the loss of the remaining normal allele (LOH) can lead to cancer.

What are some mechanisms that can lead to loss of heterozygosity (LOH)?

Mechanisms include non-disjunction during mitosis, somatic recombination, chromosome deletion, and point mutation or epigenetic silencing of the remaining functional allele.

What is knockdown in gene function studies?

Knockdown refers to reducing gene expression, often using RNA interference (RNAi) with small RNA molecules (e.g., siRNAs, shRNAs) to target and degrade specific mRNA transcripts.

What is the difference between knockout and knockdown?

Knockout involves completely deleting a gene of interest, while knockdown reduces its expression without completely eliminating it.

What is a conditional knockout?

A conditional knockout allows gene deletion in specific cells or tissues using systems like Cre-loxP recombination.

What is transgenesis?

Transgenesis is the introduction of an exogenous gene (transgene) into the genome of an organism or cultured cells to study gene effects or create animal models of disease.

What are dominant negative variants?

Dominant negative variants are mutated forms of a protein that interfere with the function of the normal protein.

What are random mutagenesis screens used for?

They are used to induce random mutations and identify genes underlying specific phenotypes of interest, a process known as forward genetics.

What is genomics?

Genomics involves studying the entire genome or transcriptome to compare gene expression levels or identify genetic variants, with RNAseq being the preferred method for transcriptome profiling.

What is proteomics?

Proteomics is the study of the entire proteome to identify proteins, quantify their abundance, and determine protein-protein interactions, often using mass spectrometry.

What is the role of model organisms in studying human gene function?

Model organisms, such as mice, are used to study human gene function and disease by modeling loss-of-function and gain-of-function mutations in orthologous genes.

What is ultrasonography used for in prenatal screening?

Ultrasonography is an imaging technique used to assess fetal development and identify structural abnormalities.

What does maternal serum screening measure?

It measures levels of specific proteins (biomarkers) in the mother's blood to assess the risk of certain fetal conditions.

What is amniocentesis?

Amniocentesis is an invasive procedure performed at 16-20 weeks to collect amniotic fluid containing fetal cells for genetic analysis.

What is chorionic villus sampling (CVS)?

CVS is an invasive procedure performed at 10-14 weeks to collect a sample of chorionic villi (placental tissue) for genetic analysis.

What is non-invasive prenatal testing (NIPT)?

NIPT analyzes cell-free DNA from the placenta present in the mother's blood to detect chromosomal abnormalities, offering a lower false positive rate than traditional serum screening.

What is the function of c-Kit?

c-Kit is a receptor tyrosine kinase involved in signaling pathways required for neural crest cell derivatives, such as pigmentation, and its ligand is stem cell factor (SCF).

What genetic conditions can mutations in c-Kit lead to?

Mutations in c-Kit can lead to Piebaldism and Waardenburg syndrome.

What are FGFRs and their role in development?

FGFRs (Fibroblast growth factor receptors) are a family of receptor tyrosine kinases (RTKs) involved in developmental processes such as bone growth and skull development. Mutations in FGFR1, 2, or 3 can lead to conditions like craniosynostosis and dwarfism, including Achondroplasia caused by FGFR3 mutations.

What is a paracrine ligand?

A paracrine ligand is a signaling molecule (growth factor) secreted by one cell that binds to a receptor on a nearby target cell, such as SCF for c-Kit or FGF for FGFRs.

What is the function of a receptor in the RTK pathway?

A receptor is a transmembrane protein that binds the ligand and initiates intracellular signaling, examples include c-Kit and FGFR.

What role do adaptor proteins play in signaling pathways?

Adaptor proteins are intracellular proteins that bind to activated receptors and recruit other signaling molecules, such as Grb2 in the Ras-ERK pathway.

What is the function of GEF in signaling?

GEF (Guanine nucleotide exchange factor) activates small G proteins like Ras by promoting the exchange of GDP for GTP, such as Sos for Ras.

How do GAPs affect small G proteins?

GAP (GTPase-activating protein) inactivates small G proteins like Ras by stimulating GTP hydrolysis to GDP; NF1 encodes a Ras GAP.

What is the role of Ras in signaling pathways?

Ras is a small G protein that acts as a signaling 'switch' downstream of RTKs, initiating kinase cascades when activated.

Describe the kinase cascade in the MAPK pathway.

The kinase cascade in the MAPK pathway involves a series of kinases that phosphorylate and activate each other, relaying the signal downstream, including Raf (MAPKKK), MEK (MAPKK), and ERK (MAPK).

What is the function of ERK in cellular signaling?

ERK (Extracellular signal-regulated kinase) is a MAPK that phosphorylates transcription factors in the nucleus, leading to changes in gene expression, such as the phosphorylation of MITF.

What is MITF and its role in development?

MITF (Melanocyte Inducing Transcription Factor) is a transcription factor downstream of Kit/MAPK signaling, involved in melanocyte development and pigmentation.

What is the role of tyrosinase in pigmentation?

Tyrosinase is an enzyme involved in melanin synthesis, acting downstream of MITF.

What is c-Myc and its significance in cell proliferation?

c-Myc is a transcription factor involved in cell proliferation and can be a target of RTK/Ras-ERK signaling and Wnt signaling.

What is the function of Shh in embryonic development?

Shh (Sonic hedgehog) is a morphogen that diffuses to create a concentration gradient, involved in embryo pattern formation, limb development, and neural differentiation.

What is the role of the Patched receptor in the Shh pathway?

The Patched receptor is a transmembrane receptor that normally inhibits Smoothened; Shh binding to Patched releases this inhibition.

How does Smoothened function in the Shh pathway?

Smoothened is a transmembrane protein that, when activated by Shh signaling via Patched, activates downstream components of the pathway.

What are Gli transcription factors and their role?

Gli transcription factors (e.g., Gli3, Gli2) are activated or repressed depending on the Shh signal, regulating target gene expression.

What are Hox genes and their function?

Hox genes are a family of conserved genes encoding transcription factors that control body plan formation along the anterior-posterior axis.