human genome abnormalities
Page 1: Introduction
Topic: Genetics, focusing on the human genome, chromosome abnormalities.
Course: Foundation Year Course, Fundamentals of Human Biology (Code: FUNBIO.21).
Lecture by: [Lecturer's name].
Page 2: Learning Outcomes
ALO 1: Define linkage in Mendelian inheritance.
ALO 2: Differentiate total linkage and crossing over effects.
ALO 3: Define polyploidy (plants) and aneuploidy (animals).
ALO 4: Describe non-disjunction during meiosis.
ALO 5: Discuss trisomy (e.g., Down’s syndrome, Klinefelter’s) and monosomy (Turner’s syndrome).
ALO 6: Discuss the importance of X and Y chromosomes in genetics.
ALO 7: Understand sex linkage operations.
ALO 8: Describe genetics of X-linked disease haemophilia A and its historical legacy.
Page 3: Linkage and Mendelian Inheritance
Humans possess 23 pairs of chromosomes, each containing hundreds of genes.
The probability of two alleles being on the same chromosome is 1:23.
Linkage occurs when two alleles are located on the same chromosome.
Mendel’s laws of inheritance apply only if alleles are on different chromosomes.
Genes on the same chromosome may exhibit linked expression.
Page 4: Linkage Characteristics
Mendelian traits appear independent as genes segregate during meiosis.
Alleles on the same chromosome cannot assort independently.
Genes on the same chromosome form linkage groups, altering expected inheritance ratios.
Page 5: The Concept of Linkage
Independent assortment has limitations due to chromosomes carrying multiple genes.
In human Drosophila models, the linkage probability is 1:4 for 4 chromosome pairs.
Linkage Definition: Tendency of alleles to assort together on the same chromosome.
E. B. Ford (1942) defines linkage in genetic terms and its implications on inheritance.
Page 6: Drosophila's Role in Linkage Studies
Morgan and colleagues established linkage in Drosophila in 1910.
William Bateson and R. C. Punnett first observed linkage in sweet peas (1905).
Page 7: Alleles in Drosophila
Normal wing allele (V) vs. mutant vestigial wing allele (vg).
Color alleles: Grey body (B) and black body (b).
Crossed heterozygous females with homozygous males to study gene interactions.
Page 8: Gamete Production in Meiosis
During meiosis, only two gamete types occur: (VB) and (vgb).
Results in a phenotypic ratio of 3:1 instead of expected 9:3:3:1 due to linkage effects.
Page 9: Total Linkage vs. Crossing Over
Examples studied so far indicate total linkage, rare cases where no crossing over occurs.
Significant crossing over occurs during meiosis due to chiasmata formation.
Page 10: Crossing Over and Multiple Recombination
Measurements have an accuracy limit of 8% due to potential multiple crossovers.
Only recombination frequency is observed; not the crossover frequency itself.
Page 11: Effects of Crossing Over
Heterozygotes can produce two recombinants, resulting in varied gamete compositions.
Calculated recombination rate example indicates a 17.1% recombination frequency.
Page 12: Gamete Frequency in Linkage Analysis
Expected proportions in independent assortment vary from those seen with complete linkage.
Examines the outcomes from backcross experiments.
Page 13: Chromosome Aberrations Overview
Chromosome number in cells is typically constant.
Types of aberrations: Polyploidy ( in plan ts 2N gets triploid 3N tetra 4N)and Aneuploidy(trisomy non-disjunction or translocation).
Polyploidy examples: triploid, tetraploid conditions in plants.
Page 14: Aneuploidy Characteristics
Defined as an abnormal number of chromosomes, either one more or one less.
due to impropper miosis in anaphase 1 meiosis anaphase 2.
Most aneuploid cells do not survive; stems from improper meiosis.
Trisomy: is rarely compatable with life excludimg 21
Monosomy is almost always lethal with x chromasome being an exception
non-disjunction ocuurs in anaphases
Page 15: Non-Disjunction in Meiosis
Non-disjunction is the failure of chromosome pairs to segregate properly.
This can occur during both meiotic divisions.
Page 16: Visualizing Nondisjunction
Normal vs. nondisjunction cases illustrated.
Non-separation of chromosomes leads to abnormal gamete production.
Page 17: Chromosome Abnormalities Introduction
Examination of different aneuploidy disorders characterized by abnormal chromosome numbers.
Page 18: Chromosomal Abnormalities and Their Disorders
Trisomy 13 (Patau syndrome): Multiple defects, often fatal by 3 months.
Trisomy 18 (Edwards syndrome): Physical and developmental abnormalities with high mortality.
Trisomy 21 (Down syndrome): Common, can involve congenital issues, increasing risk with maternal age.
Other examples include Turner syndrome and Klinefelter syndrome.
Page 19: Discussing Trisomies and Monosomies
Focus on trisomy 21
(Down Syndrome) can be detected straight from birth due to the facial features
The eyes have a disticnt upslanting fold giving the old name mongolism
other features include short neck, flat nasal bridge, low set ears,stubby hands and feet,short stature.
Klinefelter’s syndrome.
chromosme 21 has an extra copy results in heart failure, mental retardation, linked to maternal age
same features as down
Anomalies resulting from aneuploidy impact developmental outcomes.
Page 20: Down's Syndrome Characteristics
Trisomy 21 leads to heart issues, cognitive delays manifest by the first year.
may also affect intestinal tract
Page 21: Down's Syndrome: Congenital Features
Increased risk of congenital defects; emphasis on mental challenges associated with trisomy 21.
Page 22: Understanding Translocations
Translocation Types:
Reciprocal: Exchange between two chromosomes.
Non-Reciprocal: Fragmentation and addition to another chromosome.
Page 23: Risk Factors in Down's Syndrome
Age-related risks for Down's; discuss Robertsonian translocation impacts.
the fusion of the long arms of two acroentric chromosmes ( they hav short arms)
this results in 45 chromosomes in a karyotype but phenotypically is balanced
46 chromosomes with extra chromosome 21 attached to 14
Page 24: Klinefelter's Syndrome Overview
Genotype 47, XXY associated with various physical and health traits.
1:1000 male births
50% error in meiosis 1 due to failure in the psudeoautosomal region
Page 25: Clinical Traits of Klinefelter's Syndrome
Taller than average, breast development, reduced fertility and facial hair. and learning retardation
Page 26: Klinefelter's Syndrome in Adolescence
Often detected at puberty; affected individuals have various learning challenges.
Page 27: Clinical Characteristics of Turner Syndrome
Typical traits include short stature, neck webbing, and underdeveloped sex organs.
1:4000 female births
about half is a patermnal non-disjunction in meiosis 2
Page 28: Detailed Discussion of Turner Syndrome
Discuss 45, X karyotype and related developmental phenomena.
newborns show webbing of the neck and oedema of the hands and feet
growth is slow and are short with low set ears
broad chest with widely spaced nipples but underdeveloped breasts
Page 29: Turner Syndrome Outcomes
Cardiovascular issues common; average intelligence observed despite physical anomalies.
the uterus is small and the overies are absent
no mental retardation
although relatively health high spontatneous abortion rates after conception
Page 30: Monosomy in Turner Syndrome
Defined as the presence of only one X chromosome in females.
Page 31: Importance of Sex Chromosomes
Historical beliefs on sex determination and modern understanding.
Page 32: Evolution of Sex Determination
Outline of sports gender testing in history with Barr test introduction.
Page 33: Genetics of Sex Determination
Male gametes show heterogametic sex, leading to genetic variability in offspring.
Page 34: X and Y Chromosome Characteristics
Notably different sizes of X and Y chromosomes; implications on gene expression.
Page 35: Mechanism of Sex Differentiation
Timeline of sex differentiation relative to chromosome presence and hormonal influence.
sex of a gamate isnt deffinate until about 6 weeks
in the absence of the Y the genitelia remains female ( swyer sydrome: a mutation on SRY(in the short arm))
in the presence of y chromosomes leads to the developmet of testes and produce testostrone
Page 36: Sex Phenotypes in Other Species
Mention of different sex determination mechanisms in various organisms.
tapering penises
proctandric hermaphroditism
Page 37: Sex Linkage Mechanisms
Understanding total sex linkage on X chromosome; implications for female carriers.
Total sex linkage is when a woman can inherit a condition and pass it to their sons without being affected themselves
Caused by a single gene pair dominant in male recessive in female
Page 38: Genes on Sex Chromosomes
Examination of Y-linked and X-linked traits, emphasizing inheritance patterns.
Most x-linked genes are recessive in the female and carried on the x chromosme
y Borne Genes is a condition expressed in males handed down to all sons
hairy ear rims are possible y borne genes
Page 39: Haemophilia A Genetics
An analysis of severity and inheritance patterns related to haemophilia A.
Blood condition where it does not clot properly x-linked mutation
1:10,000 male births
extremely rare in females 1:100 million
1:5,000 women are heterozygous
Page 40: Pedigree and Estimating Risk
Calculation of inheritance patterns for haemophilia A through carrier dynamics.
phenotypic ration of 3:1 half of the sons are hemophiliacs but non of the daughters
Page 41: Historical Impact of Haemophilia A
Case study of haemophilia within the British royal family, tracing lineage patterns.
Page 42: Family Dynamics in Haemophilia A Treatment
Consequences of marrying outside the family context in terms of genetics.
haemophilic son with normal homozygote mom will result in none of the sons having the condition but all the daughters are heterozygotes meaning carriers