Molecular_Mechanisms.pptx
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Synthesizes new DNA strands
Molecular Mechanisms in Genetics and Genomics
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Directional movement (5' to 3')
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Course Overview
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Source: Based on Human Genetics and Genomics by
Bruce R. Korf (2013)
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Telomerase:
Comprehend molecular processes of genetic
information transfer
Understand DNA replication, RNA
transcription, and protein translation
Explore the roles of codons and anticodons
DNA Replication: Fundamental Mechanism
Definition and Characteristics
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Core Concept: Precise duplication of DNA molecules
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Key Features:
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Semi-conservative replication mechanism
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Occurs during S-phase of cell cycle
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Ensures accurate genetic information
transmission
Detailed Replication Stages
1. Initiation Phase
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3. Termination Phase
Primary Objectives:
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Critical Enzymes and Proteins:
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Helicase: Unwinds DNA double helix
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Topoisomerase: Prevents DNA supercoiling
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Single-strand Binding Proteins: Stabilize
exposed DNA strands
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DNA Ligase: Connects Okazaki fragments
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Extends chromosome telomeres
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Crucial for certain cell types
Transcription: RNA Synthesis
Definition and Characteristics
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Core Process: Converting DNA information to RNA
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Location: Nucleus (in eukaryotic cells)
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Primary Enzyme: RNA Polymerase
RNA Types
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Messenger RNA (mRNA)
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Ribosomal RNA (rRNA)
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Transfer RNA (tRNA)
Transcription Stages
1. Initiation
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RNA Polymerase binds to promoter region
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DNA locally unwinds
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Exposes template strand
2. Elongation
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RNA synthesized complementary to DNA template
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Key Molecular Substitution:
Origin of Replication (ORI): Starting point
for DNA duplication
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Uracil (U) replaces Thymine (T)
3. Termination
2. Elongation Phase
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RNA Polymerase releases transcript
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Pre-mRNA processing:
Key Enzymes:
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Primase: Synthesizes RNA primers
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DNA Polymerase III:
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Splicing
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5' Capping
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Polyadenylation
Translation: Protein Synthesis
Definition and Characteristics
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Core Process: Converting mRNA to proteins
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Location: Cytoplasm (in eukaryotic cells)
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Key Components:
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Ribosomes
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Transfer RNA (tRNA)
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Messenger RNA (mRNA)
Genetic Code Fundamentals
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Codons: Three-nucleotide sequences
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Anticodons: Complementary RNA sequences
Molecular Interaction Diagram
Key Takeaways
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Molecular processes are interconnected
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Precision is crucial in genetic information transfer
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Each stage involves specific enzymes and molecular
mechanisms
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Genetic_Disorders_Presentation (1).pptx
Genetic Defects and Chromosomal Disorders Study
Guide
Clinical Manifestations
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Overview of Chromosomal Disorders
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Definition: Genetic abnormalities resulting from
numerical or structural chromosome changes
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Primary Causes:
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Nondisjunction
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Deletions
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Unbalanced translocation
Developmental Impacts:
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Loss of TERT gene affects brain
development
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Distinctive high-pitched cry
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Intellectual disability
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Microcephaly
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Growth delays
Translocations
Klinefelter Syndrome
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Mosaicism
Genetic Configuration
Down Syndrome (Trisomy 21)
Genetic Characteristics
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Karyotype: 47,XX,+21 or 47,XY,+21
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Occurrence Breakdown:
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Karyotype: 47,XXY
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Origin: Nondisjunction during gametogenesis
Physiological Consequences
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Nondisjunction: 95%
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Robertsonian Translocation: 3-4%
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Mosaicism: 1-2%
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Key Mechanisms
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Gene Overexpression
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Extra chromosome 21 impacts:
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Brain development
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Heart formation
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Immune function
Hormonal Disruptions:
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Androgen deficiency
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Testicular dysfunction
Physical Characteristics:
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Tall stature
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Gynecomastia
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Infertility
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Learning disabilities
Chronic Myelogenous Leukemia (CML)
Genetic Mechanism
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Alzheimer's Risk: Increased due to extra APP gene
dosage
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Chromosomal Translocation: t(9;22)(q34;q11)
Cri-du-chat Syndrome
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Fusion Gene: BCR-ABL1 creation
Disease Progression
Genetic Profile
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Defect: Deletion of chromosome 5 short arm (5p-)
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Causes:
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Chromosomal breakage
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Cellular Changes:
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Unregulated tyrosine kinase activity
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Increased myeloid cell proliferation
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Stages:
Additional Complications:
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Chronic phase
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Congenital heart defects
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Potential progression to blast crisis
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Aortic coarctation
Triple X Syndrome
Diagnostic and Management Strategies
Genetic Configuration
Key Diagnostic Approaches
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Karyotype: 47,XXX
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Cytogenetic testing
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Origin: Nondisjunction during meiosis
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Comprehensive genetic screening
Developmental Characteristics
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X Chromosome Compensation:
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Lyonization (X-inactivation)
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Some X-linked genes escape inactivation
Treatment Principles
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Symptom management
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Individualized intervention strategies
Comprehensive Disorder Classification
Chromosomal Abnormality Types
Clinical Outcomes:
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Mild cognitive deficits
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Normal puberty
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Down Syndrome
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Typically normal fertility
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Triple X Syndrome
Turner Syndrome
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Trisomies:
Monosomy:
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Genetic Profile
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Karyotype: 45,X or Monosomy X
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Variations:
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Cri-du-chat Syndrome
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45,X/46,XX mosaicism
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Chronic Myelogenous Leukemia
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45,X/46,XY mosaicism
Physiological Impacts
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Turner Syndrome
Structural Abnormalities:
Underlying Mechanism
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Core Concept: Gene dosage imbalance causing
developmental and physiological disruptions
SHOX Gene Loss:
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Short stature
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Skeletal abnormalities
Genetic_Disorders_Expanded_Presentation.pptx
Reproductive Consequences:
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Ovarian dysgenesis
Genetic Defects and Chromosomal Disorders Study
Guide
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Estrogen deficiency
Overview of Chromosomal Disorders
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Infertility
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Definition: Genetic abnormalities resulting from
numerical or structural chromosome changes
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Primary Causes:
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Consequences:
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Nondisjunction
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Intellectual disability
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Deletions
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Microcephaly
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Translocations
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Growth delays
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Mosaicism
3. Klinefelter Syndrome
Specific Chromosomal Disorders
Genetic Configuration: 47,XXY
1. Down Syndrome (Trisomy 21)
Key Characteristics:
Genetic Profile:
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Extra X chromosome in males
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Chromosome Configuration: 47,XX,+21 or 47,XY,+21
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Origin: Nondisjunction during gametogenesis
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Occurrence Breakdown:
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Clinical Features:
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Nondisjunction: 95%
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Tall stature
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Robertsonian Translocation: 3-4%
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Gynecomastia
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Mosaicism: 1-2%
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Infertility
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Learning disabilities
Key Mechanisms:
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Gene overexpression on chromosome 21
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Impacts:
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Mechanism: Androgen deficiency from testicular
dysfunction
4. Triple X Syndrome
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Brain development
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Heart formation
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Immune function
Genetic Profile: 47,XXX
Mechanisms:
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Lyonization (X-chromosome inactivation)
compensates extra chromosome
2. Cri-du-chat Syndrome
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Some X-linked genes escape inactivation
Genetic Defect:
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Outcomes:
Increased Alzheimer's risk due to extra APP gene
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Chromosome Deletion: Short arm of chromosome 5
(5p-)
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Caused by:
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Chromosomal breakage
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Unbalanced translocation
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Mild cognitive deficits
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Normal puberty
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Typically normal fertility
5. Turner Syndrome
Genetic Configuration: 45,X or Monosomy X
Clinical Manifestations:
Characteristics:
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TERT gene loss affecting brain development
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Distinctive high-pitched cry
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Complete/partial X chromosome loss
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Potential mosaicism: 45,X/46,XX or 45,X/46,XY
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Unique facial characteristics
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Key Impacts:
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Cardiovascular abnormalities
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Intellectual disability
SHOX gene loss causing:
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Short stature
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Strong verbal skills
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Skeletal abnormalities
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Overly friendly personality
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Ovarian dysgenesis
9. Prader-Willi Syndrome
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Estrogen deficiency
Genetic Mechanism:
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Congenital heart defects
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Paternal 15q11-q13 deletion
6. Edward Syndrome (Trisomy 18)
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Maternal uniparental disomy
Clinical Manifestations:
Genetic Profile: 47,XX,+18 or 47,XY,+18
Clinical Features:
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Hypothalamic dysfunction
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Severe developmental delays
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Appetite regulation issues
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Extensive multi-organ system impacts
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Symptoms:
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Congenital heart defects
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Severe obesity
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Prognosis: Very low survival beyond infancy
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Hypotonia
7. Patau Syndrome (Trisomy 13)
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Intellectual disability
Genetic Configuration: 47,XX,+13 or 47,XY,+13
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Growth hormone deficiency
Developmental Impacts:
10. Angelman Syndrome
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Brain and facial development disruption
Genetic Origin:
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Characteristics:
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Microcephaly
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Cleft lip/palate
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Congenital heart defects
High infant mortality rate
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Maternal 15q11-q13 deletion
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Paternal uniparental disomy
Neurological Characteristics:
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UBE3A gene involvement
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Key Features:
8. Williams Syndrome
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Severe intellectual disability
Genetic Defect: 7q11.23 chromosome deletion
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Ataxia
Unique Features:
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Frequent smiling/laughter
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ELN gene (elastin) loss
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Minimal speech development
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Distinctive Traits:
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Seizures