1. DNA replication of spermatogonium (germ cell) starts at puberty to create primary spermatocytes (4N)

2. Primary spermatocytes (4N) complete meiosis 1 to form 2 secondary spermatocytes (2N)

3. Secondary Spermatocytes (2N) complete Meiosis II to form spermatids (1N)

4. Spermatids remove unnecessary cellular comparments

5.Spermatids undergoes spermiogenesis
to become spermatozoa

6. Spermatozoa undergo capacitation in the female reporductive tract (change in glycoproteins, lipids, ion channels, intercellular pH).

1. Primodial germ cells migrate to developing gonads and undergo mitosis to become oogonia

2. As Meiosis I starts, DNA is replicated and Oogonia become primary oocytes (4N)

3. Prophase I starts, both crossing over and independant assortment occur, oocytes arrest at diplotene (all prior to birth)

4. Oocyte maturation- at time of ovulation (puberty) the oocyte completes Meiosis I. One set of homologs (2N) becomes 1st Polar Body, the other set becomes a secondary oocyte (2N) which Arrests at Metaphase II.

5. Fertilization triggers the completion of meiosis II. One set of chromatids (1N) form the 2nd Polar Body , the other set become the Ovum (1N) and fuses with the Sperm Nucleus to become the Zygote.

69 or 92 chromosomes

Triploidy - Child may be born alive, but will die soon after birth

Triploidy is when there is a third copy of the 23 chromosomes (so 69 total). It is usually considered a results of Dispermy (two sperm fertilizing one ovum)

Fetus usually have problem associated with placenta, and undergo spontaneous abortion (although it is possible to survive to birth).

NO, TRIPLOIDY (69 CHROMOSOMES) IS NOT THE SAME AS TRISOMY(47 CHROMOSOMES)

"not true set of chromosomes"

cells that contain an extra or are missing a chromosome. Exp: monosomy (45 chromosomes) or trisomy (47 Chromosomes)

Aneuploidy results from non disjunction during Meiosis (anaphase I or II)

Can result from the lack of homologous recombination.

In meiosis I nondisjuntion you have one maternal chromosome and one paternal.

In meiosis II nondisjunction you have two paternal or two maternal chromosomes.

 Meiosis I is more common than Meiosis II non disjunction

50% (during 1st trimester)

20% (during 2nd trimester)

1 in 150 live births (0.67%)

At metaphase

Trisomys, Monosomys, etc.

Centromere is at end of chromosome

exp = 13,14,15,21,22

Used to examine chromosomal reaarangements, copy number

Specifically important for translocations

Detect Loss of Function and Gain of Function

Shows duplications and deletions

Does NOT detect balanced abnormalities

Literally means 'with blood.' represented by a double line on pedigress.

Think Consanguinity = Cousin Couples (upto 2nd degree)

Fun fact: Charles Darwin was part of a 'cousin couple' (first degree)

Difference between Gene and Allele

A gene is simply a protein encoding DNA sequence

An Allele is a variant of a gene.

So if you take gene 20 from dad, and gene 20 from mom, they are the same gene, but have different alleles.

Protein is made and either increases protein activity or the amount of protein

Duplications

Missense

Promoters

Splicing

No protein is made or protein does not work properly

Nonsense, Frameshift, missense, promoter, splicing, deletion

Codes for the phenotype that is expressed when it is heterozygous with another allele

(Bb) where B is brown and is the expressed (dominant phenotype)

Does NOT skip generations (vertical transmisson)

Males and female affected equally

Transmited by males and females

CAN include Father to son transmission

Can Skip Generations with multiple affected siblings (horizontal transmission)

Transmitted by phenotypically 'healthy' parents to affected offspring

Occurs in higher frequency in consanguinous mating (like Darwins kids being infertile)

Affects male and females equally

1. Autosomal Dominant

2. S/s - Aortic root aneurysm or dissection

Ectopic lens (abnomal lens position)

Tall stature, arm legth > height (Kevin Durant)

arachnodactyly (long slinder fingers) with joint hypermobility

1. Autosomal Dominant (Even tho considered dominant two copies of the NF1 gene must be altered to trigger tumor formation in neurofibromatosis type 1, if you have one mut you almost always get the other later)

2. S/s- Multiple Benign Fleshy Tumors (nuerofibromas)

Irregular Pigmented skin (cafe au lait)

Benign Tumors on Iris (Lisch Nodules/hamartomas)

MR

CNS Tumors

Development of Ca of CNS or muscle (only if

AKA Herdiatary Motor and Sensory Nueropathy Type 1 (HMSN1)

1. Autosomal Dominant

2. S/s- Symptoms present by age 20

Slow progressing weakness

Hammer Toe

Atrophy of the distal Leg muscles

Mild sensory impairment

Foot deformities

weakness in hand muscles (late sign)

decreased/absent reflexes

Upper extremity ataxia and tremor

Gene Duplication; Gain of Function Mutation

Gene: PMP22

Function of Gene: produces Peripheral myelin protein 22 a important portective protein that is part of myelin. When there are two copies of PMP22, too much of the protein is produced, which prevents it from being processed. This leads to less functional PMP22, which then cause demylenation, which leads to nerve damage/ s/s of Charcot-Marie Tooth disease.

Type of mutation: missense or deletion

 Gene: Fibrillin-1 (FBN1)

Function of gene: essential for the formation of elastic fibers found in connective tissue

Leads to abnormal TGF-Beta  signalling ( helps to control the growth and division (proliferation) of cells)

Allelic Heterogeneity(thousands of mut lead to same disorder)

Pleiotrophy - Multiple phenotypic effect from a single allele or pair of alleles (the effects not thought to be related.

3. Loss of function mutation

4. Gene is NF1

Function of Gene: making a protein called neurofibromin, which supresses tumors by turning off RAS (a protein that stimulates cell growth and division).

Is a neg regulator of the ras signaling pathway

5. Variable Expressivity - can have same mut/dz but have different levels of severity

1. Autosomal Dominant

2. S/s - Coloboma (eye defect)

Heart Defects

Atresia of the choanae (narrowing of nasal airway)

Retardation of Growth

Genital Underdevelopment d/t hypogonadatrophic hypogonadism

Ear Abnormailities

Type of mutation: Usually Loss of Function mutation

1. Autosomal Recessive

2. S/s - Increased Na in Sweat

Pancreatic Insufficiency

Thick Dehydrated Mucus

Fibrotic Lungs with Reoccurent Infections

Hypertonic GI, Resp, and Reproductive Epithelial cells.

Type of Mutation:

Usually deletion,  Loss of Function mutation

Gene:CFTR - Regulates the flow of Cl ions in and out of cells.

DeltaF508 is most common

Mutation in this gene leads to misfolding of the protein which leads to early degradation.

Hemoglobinopathies

Thalassemia  (dominance/symptoms)

1. Autosomal Recessive

2. S/s - Reduced level of Adult Hemoglobin (HbA)

Hemoglobinopathies Thalassemia (Type of Mutation/Mutation Gene function)

Type of Mutation:

α-thalassemia: mutation decreasing α-globin

β-thalassemia: mut decreasing β-globin           

β° - thalassemia: complete absence of β-globin  (frameshift, nonsense, splice mutation)                        

 β⁺- thalassemia: reduced amount of β-globin (splice mutations, promoter mutations)

Gene: HBA1 or HBA2 (hemoglobin, alpha 1 or 2); HBB (hemoglobin, beta) gene

Function: Make up the subunits of hemoglobin (2 alpha globin, 2 B globins)

Heterozygotes = Thalessemia Minor

Homozygotes = Thalessemia Major

Heterozygote screening in Cyprus and Sardinia lowered incidence by 65-80%

1. Autosomal Recessive 

2. S/s - joint pain, fatigue, swelling hands and feet, jaundice as a result of vaso-occulsions

3. Missense Mutation

4. Gene - Glu6Val mut in β-globin chain 

Gene function - substitutes a valine for a glutamine at position 6; This changes how the protein folds when O2 is present

Heterozygous individuals still get some symptoms.

Positive selection w/ Malaria Heterozygote advantage.

1. Autosomal Recessive

2. S/s - Normal infant till 3-6 months then has nuerological deteriation

Higher incidence in Ashkenazi Jews* (Eastern European Jews...)

Cherry Red Spot on Retina

*heterozygote screen lower incidence 65-80%)

Type of mutation - Frameshift Mutation

Gene: HEXA (Hexoaminadase A)

Function of Gene: Helps form a enzyme that breaks down GM2 ganglioside. Mutation leads to inability to breakdown GM2. So this substance builds up to toxic levels, particularly in nerve cells in the brain and spinal cord, and causes progressive nuerological damage.

1. Incomplete Dominance

2. S/s - Dwarfism,

Short limbs,

long and narrow trunk,

macrocephaly w/prominent forehead.

Normal intelligence,

some impaired motor skills

If both dominant genes expressed it is a lethal phenotype (i.e. AA is lethal and not viable)

Type of Mutation: Gain-of-Function mutation

Gene: Caused by Gly380Arg mutation in FGFR3 gene

Gene function: Encodes a tyrosine receptor that intiates a signaling cascade that controls bone growth and differentiation. The Gly380Arg mutation leads to constitutively active receptor and inhibits chrondrocyte proliferation.

Assortive Mating - only 66% Viable for the gene as a double mutation is lethal/nonviable

The classic example is Blood groups. The phenotype for more than one allele is shown at the same time.

Neither Allele blocks the others phenotype

A - α1.3-Nacetylgalactosamyl transferase

B - α1.3-Ngalatcosyltransferase

O  - no transferase ativity

When a new (de novo) mutation arises in one cell in the early embryo.

So the mutation is only in part of the cells somatic cells. Could be viable depending on how many cells are affected.

Exp would be partial Trisomy 9

Down Syndrome / Trisomy 21

SYMPTOMS:

- brachycephaly (flat head)

- flat Nasal Bridge

- brushfield Spots on margin of iris

- wide gap b/w toes 

- single transverse palmar (simian) crease

- epicanthal Folds

- developed hearing loss

- risk of early Alzheimer's

- Pleiotropy

- Non-Disjunction

-Chromosomal Analysis shows three 

   copies of the 21st chromosome

- Non Disjunction @ Meiosis II

- Malformations of Brain

- Rocker Feet

- Microcephaly

- Low-set-ears rotated backwards

- Prominent Occiput

- Poor prognosis --> few survive first year

- Chromosomal Analsys shows 3 copies of

  chromosomal 18

- Non-Disjunction

- Holoprosencephaly (failure of braint to develop)

- Cleft lip / cleft palate (malformation)

- Renal Abnormalaties

- Cutaneous scalp defects

- The worst prognosis of of other tirsomy syndromes

- Largest cause of spontaneous abortion

- Chromosomal analysis reveals three copies of

  chromosome 13

- Nondisjunction of Sex chromosomes

- No Bar Bodies

- Most Common Isochromosome

- Female

- Webbed Neck

- Wide spaced nipples

- Renal / cardiac defects

- Edema of feet at birth

- Shortned fourth metacarpal

- Otitis Media (hearing loss)

- gonadal dysgenesis

- Microaray analysis: found no duplications

- Non-Disjunction Sex Chromosomes

- Errors in Paternal Meiosis I (sperm brings X&Y)

- one bar body

- No syptoms prior to puberty

- tall

- thin

- hypogonadism discovered @ puberty

- underdeveloped secondary sex characteristics

- infertility

- Most frequent for of sex aneuploidy

- Cleft Palate

- Identifiable = Look of Face

- FIRST SIGN: behavior problems

- Thymic Hypoplasia --> increased susceptibility to

                                      infections 

- ADD & ASD(Autisim Spectrum Disorder)

- Hypoparathyroidism

- Hypocalcemia --> Convulsions

- GENE = TBX1

- Chromosome = 22q11

- Microdeletion

- affects apoptosis of embryonic development

   associated w/Cardiac Defects (80% have ♥ defects)

- Diagnosed by FISH

Cri-du-Chat

Syndrome

- Laryngeal Defects

- Catlike High Pitched Cry

- Microcephaly

- Hypotelorism

- Broad Nasal Root

- Downslanting Palpebral Fissure

- High Arched Palate 

- 5p Deletion

Wolf-Hirshhorn 

Syndrome

- Wide spaced eyes

- short distance b/w nose and lips

- downturned mouth

- Hypotonia

- Strong Social Skills

- 4p16 deletion

- Cocktail Party Personality

- Poor visospacial abilities

- Low IQ (40-80)

- Short palpebral fissure

- short nose w/depressed bridge

- full lips/cheeks

- wide-spaced teeth

- microdeletion 7q11.23

-DX: by FISH

FH

(Familial Hypercholesterolemia)

- Autosomal Dominant

- Allelic Heterogeneity (many mutations--> same disease)

- Incrased LDL in blood --> coronary artery disease

- Mutations in LDLR affecting synthesis, transport,

   binding, clustering, and recycling of LDL

- Heterozygotes --> 1/2 normal LDLRs asymptomatic

                               until 30-40 yrs

- Homozygotes --> no normal LDL, xanthomas by 4yrs

                             old, severe hypercholesterolemia  @

                             birth

-TX: liver transplant /  conventional therapies

Vitamin-D Resistant

Rickets

- Slow Growth

- Short Stature

- Bone Abnormalaties

- Genu Varum Legs

- X-Linked Dominant

- Gene: PHEX

- Low Serum Phophate

- X-Linked Dominant

- MECP2

- Wringing of Hands

- Intelectual Disability

- MECP2 Protien binds methylated DNA (CG regions) 

- No MECP2 --> improperly expressed genes during brain

                        development

- Lethal in Males

- X-Linked Recessive --> 50% chance of "son" affected

                                 --> 25% chance of a "child" 

- Severe bleeding wounds

- hemorrhages in joints (hemarthroses) / muscles,

   intracranial 

- Bruising

- Clotting Factor VIII malfunction

- TX: clotting factor VIII

DMD

(Duschenne Muscular Dystrophy) 

- Out of Frame Deletion

- X-linked recessive

- DMD franshift Mut --> deletion

- Increased Kreatine Kinase Activity

- No Dystrophin produced

- Missing Exons 45-54

- Gower Maneuver

- Delayed motor skills (walk @ 18 months)

- 95% get ♥ disease

- more severe than Becker (in frame deletion)

- DX: by genetic testing

- X-linked Recessive

- Deletion

- Red-Green condes on X w/similar sequences cause

  errors during homologous recombination --> deletions

- X-linked Recessive

- Gene: SLC9A6 & NHE6 (Na/H Exchange)

- Inability to speak and walk

- Ataxia

- Open Mouth

- Abnormal eye movements

- Happy

- X-Linked Recessive

- High Percentage of Manifesting Heterozygoes 

- Maternal Anticipation

- CGG repeats in 5'UTR of FMR1 gene

       * Norml < 55  / Premutation 55-200  /  Mutation > 200

- GENE: FMR1 (gene silencing via methylation) --> blocks

              Translation 

- Most Common Inherited Form of Intellectual Disability

Fragile X Syndrome

Symptoms

- Intelectual Disability

- Shy 

- Hyperactive

- Big, Forehead, Jaw, Ears

- @-Birth = Macrosomia (excessive weight) &  

   macrocephaly

- @ Puberty = Abnormally Large Testicles

Huntington's Disease

(HD)

- Autosomal Dominant

- Paternal Anticipation

- Unstable Repeats in CAG --> Incr. Glutamine Residues

       * > 40 = Disease

       * 36-39= can develop later in life

       * < 60 = Juvenie HD

- Gene: HTT

- Protein: Huntington's Protein

- Inverse correlation b/w # of repeats and age of onset

Huntington's Disease (HD)

SYMPTOMS

- ONSET: Clumsiness, agitation, personality changes,

                 depression

- LATER: motor disturbances-jerky, brief, involuntary

               movements in face and upper arms

 Progressive decrease in attention/learning/memory

--> dementia

- Gene: DMPK = Protein Kinase

- Unstable repeats in CTG 3'UTR

- errors in splicing mRNA

SX:

- Progressive Muscle deteriorarion Myotonia

- Inability to relax

- Arrhythmias

- Develeoped Insulin Resistance

- Facial Features Progress

MERRF Disease

(Myoclonic Epilepsy & Ragged-Red Fiber Disease)

- Mitochondrial Inheritance

- Mutaion A--> G subsitution at locas 8344 in gene  

                       encoding tRNAlys

- Gene: tRNAlys

- Homoplasy (all or none mutated)

- Heterplasy ( mixed mitochondria)

SX:

- Twitching Muscle Spasms

- Seizures

- ataxia

- Ragged-Red-Fibers (only occurs w/Mito Inheritance)

- Muscle Biopsy shows ragged red stuff

MELAS Syndrome

(Mitochondrial Encephalomyopathy Lactic Acidosis &

Stroke-Like Episodes)

- Mitochondria Inheritance

- Point Mutation

- tRNAleu

- <1% chance of affected father passing to daughter

SX

- SX appear in Childhood

- Muscle Weakness & Pain

- Headaches

- Vomiting

- Seizures

- Strke-Like Episodes --> damage brain

- Mitochondrial Inheritance

- Point Mutation

- Gene: MT-ATP6 (involved in Oxidative Phosphorylation)

- affected father has  <1% chance of passing to

  daughter

- Juvenile Subacute Necrotizing Encphalomyopathy

SX

- Profressive loss of psychomotor skills

- Vomiting

- Diarrhea

- Dysphagia (difficulty swallowing--> failure to thrive)

- Weak muscle tone

- Patches of damaged tissue in brain

- death with-in a couple years

LHON

(Leber's Hereditary Optic Neuropathy)

- Mitochondrial Inheritance

- Point Mutation

- Gene: ND4 Gene

- involved in Complex-I o f ETC (oxidative Phosph.)

- Mostly in males

SX

- SX appear teens to 20

- Blurry Vision

- Vision Loss

- Movement disorders

- Cardiac  Conduction Defects

- Maternal Imprinting

- MUPD15

- Chromosome 15q11-q13

SX

- Obesity

- Small feet & Hands

- seizures

- Severe Hypotonia (can't hold head up)

- feeding difficulties early in infancy

- Scoliosis gets severe fast

- Excessive eating 

- Severe Intelectual Disability

- Paternal Imprinting

       * 2 imprinted blanks from father (if spontaneous)

       * Chromosomal deletion from mother

- PUPD15

- Chromsome 15q11-q13

SX

- Unusal facial appearance

- Short stature

- severe intelectual disability

- spasticity

- seizures

- Extremely Happy Personality

Beckwith-Wiedemann

Syndrome

- Paternal Imprinting   

       * 2 imprinted blanks from father

- PUPD11

- Chromosome 11

SX

- Macrosomia

- Macroglossus

- Umbilical hernia

- severe hypoglycemia

- develop malignant neoplasms of kidney, adrenals & liver

Silver-Russell 

syndrome

- Maternal Imprinting

- MUPD7

- Chromosome 7

SX

- Poor appetite --> hypoglycemia

- Small triangluar face

- Small Jaw

Digenic Retinits Pigmentosa

(DRP)

- Multifactoral Inheritance

       *need at least heterzyogocity for mutation w/both

        genes peripherin and ROM1 to have disease

- Gene: ROM1 Peripherin

- Vision Loss when one mutant allele for both genes

- Encodes photo receptors

- Multifactoral Inheritance

- APOE (Apolipoprotein E) Presentin 1&2

- Amyloid-beta-precurrsor Protein (APP) cleaved

   improperly --> beta amyloid plaques

-Three Variants = ε2, ε3, ε4

- two ε4s = 98% chance Alzheimers in 65-74 y

   w/symptoms of dementia

- Autoimmune Destruction of beta-cells in Pancreas

  (can't make insulin)

- Multifactoral Inheritance

- 12 Different HLA ALLELES

- Qualitative Phenotypes (disease or no disease)

- 1/500 caucasians @ birth

- λ_sib = 7% /.2% = 35

- Multifactoral Inheritance

- TCF7L2

- PPAR-gamma

- 0.9 heritability

- Risk Factors: Family HX & Obesity

- LOF mutation in Leptin or Receptor

- Gene: LEP

- Heritibility = 0.6-0.8

- Leptin = Hormone regulating satiety

- Alcoholism Proteins:  ADH & ALDH

- Addiction Proteins:   GABA

- Heritability:

       *Type 1 = 0.21

       *Type 2= 0.80

- Gene: NOD2

- Protein: Nucleotide Oligomerization Domain Protein

               = responsible for binding bacterial cell walls &    

                  triggering inflamatory response

SX

- Abdominal Pain

- Cramping Diarrhea

- bloody stool

- transmural ulceration

- granulomas of the GI tract

- fistulas

- inflammation of joints, eyes, skin

- Genes: DTNBP1

             NRG1

             G30

- Monozygotic Twin = 44.2% risk

- Dizogotic Twins = 12.1% risk

SX:

- Delusions

- Hallucinations

- Retreat from Reality

- Gene: SHH

- affects DIFFERENTIATION

- Autosomal Dominant

- LOF mutation

- has Variable Expressivity

- Starts in Notochord --> affects neuro development

- Intertwined w/limb development and FGF8

SX:

- Holoprosencephaly (Failure of midface & forebrain to

                                  develop)

- Leads to cleft lip & palate

- Hyper telorism (eyes together)

- absence of forebrain structures

- Malformation = intrinsic abnormalities of genetic

                           programming

- GLI3 - short, truncated

- only REPRESSES gene expressin

SX:

Extra fingers/toes (fused)

- Malformation

- More severe

- Autosomal Dominant

- GLI3 - LOF Mutation = more severe than Pallister-Hall

SX:

- Extra fingers / toes (fused)

- widely spaced eyes,

- macrocephaly

- LOF Mutation

- Gene: CREBBP (transcriptional activator)

SX

- Short stature

- Beaked Nose

- broad terminal phalanxes of big toe/thumb

- delayed bone maturity

- cardiac defects

- Autosomal Recessive

- LOF mutation

- Gene: WNT3 --> Req'd for ant./post. axis formation

SX:

- missing all 4 limbs

- malformations of face, head, heart, nervous system, &

   skeleton

- Autosomal Recessive

- Gene: CDMP1 = cartilage derived morphogenetic protein 1

                                 = (TGB Family)

- Everything is short

- brachydactyly (short fingers and toes)

- knob-like fingers

- HOXD13 Mutation 

- Incomplete Dominance

- affects differentiation in ebryonic development

- ant./post. axis & development of limbs

- Heterozygotes = less severe sx

- Homozygotes = more severe sx

- 3'UTR similarities b/w flies/mice/humans

- contains a DNA binding motif called homeodomain 

                                                           (homeobox)

- GOF mutation --> poly-alanine residues

       * normal = 15 alanines

       * mutation= 22-24 alanines

SX:

- interphalangeal webbing 

- extra digits

- Autosomal Dominant

- LOF mutation affecting transcription factor

- Gene: TBX5 --> req'd for organogenesis & axis

                           formation for upper limb

SX

- Triphalangeal thumbs

- Carpal bone abnormalities

- short forearm

***child w/ above sx = _____- _____ Syndrome

       Adult w/ above sx= Drug induced

                                     (drug  no longer on maket)

Miller Dieker

Syndrome

- Autosomal Dominant

- Affects MIGRATION of embryonic development

- LOF mutation

- Gene:  LIS1 on 17p --> affects waves of cortical

                                     neurons. So, lack of correct

                                     migration of cell types in brain

SX

- Lissencephaly (smooth brain)

- Thickened hypercellular cerebral cortex w/undefined

   cellular layers

- DEFORMATION (extrinsic factors on fetus)

- result of LOW AMNIOTIC FLUID

SX

- Club Foot

- Arthrogyposis-congenital joint contractures

- Hip dysplasia

- potter sequence

TX: correct w/braces & PT

- Disruptions

       (destruction of irreplaceable normal fetal tissue)

- 9th-38th week of fetal development

1. MALFORMATION

2. DISRUPTION

3. DEFORMATION

1. intrinsic abnormalaites 3rd-9th weeks of development

2. amniotic bands 9th-38th weeks

3. extrnisic factors (i.e. low amniotic fluid)

- a sequence that affects one organ system

   w/pleiotropic effects

- E.G. 

   renal abnoramalities --> Low amniotic fluid --> compressed fetus --> potter

                                          (oligohydramnios)                                         facies

SX = compression of fetus --> shmusched face 

Ellis-van Creveld

Syndrome

- Autosomal Recessive

- made prevalent by consaguinity

- Gene Mutations: EVC & EVC2

- FOUNDER EFFECT

- Amish Community / Lancaster County, PA

- Example of Variable Expressivity

SX

Cleft lip/palate,

polydactyly,

limited range of motion,

short limbs,

short stature,

sparse/absent/fine hair,

tooth abnormalities.          

- positive selection for HOMOzygotes

- B/C ΔCCR5 aids in HIV entering cell, homozyogote

   mutants = resistant to HIV

- ΔCCR5 mutation --> no chemokine receptor 5 protien

- prominent in Northern Europeans & Skandinavians

Sickle Cell 

Pisitive selection

- positive selection for HETEROzygotes

- Individuals heterozygous for sickle cell trait are

   resistant to Malaria

Cystic Fibrosis 

Positive Selection

- positive selection (selective advantage) for

   HETEROzygotes

- Heterozygotes = 50% less CFTR --> selective

   advantage against Cholera

- Assortive Mating

- Autosomal Recessive & Dominant

- Chromosome 13

- Gene: GJB2 --> encodes connexin-26 proteins involved

                           in gap junctions

- 1/1000 chidlren affected

- 80% nonsyndromic deafness

- Mutations in >30 genes --> deafness 

= Locus Heterogeneity = many genes/mut.--> one disease

- RECESSIVE ALLELES that cause Deafness:

* 30delG -  Caucasions

*167delT - Ashkenazi Jews

* 235delC - Japenese

Define

1.Stratification

2. Assortive Mating

1. groups have higher proportion of a mutated allele

2.  seeking an individual with a specific trait