Pedigrees + Inheritance Disorders

Pedigree, trait, disease

__ are general graphical depiction of related individuals

• Determine inheritance pattern of a __ or __

Autosomal Dominant Disorder

Heterozygotes (Aa) are affected with some offspring affected, others not

Autosomal Recessive Disorder

Most affected children have carrier parents that are heterozygotes (Aa)

X-linked Dominant Disorder

If male has trait, all daughters are affected as well as affected male’s mother

X-linked Recessive Disorder

If female has trait, all sons are affected as well as father

Equal, autosomal dominant

Pedigree Interpretation

• If affected males and females are approximately __, choose between autosomal dominant or autosomal recessive

  • If every affected child has at least ONE affected parent → __ __

Females, X, survival

For X-linked dominant disorders

• They are more “common” in __ (males/females)

• 2nd _ chromosome buffers effects of these disorders for females

• Given males with a lower __ rate from these disorders → Not represented

Males, X, 

For X-linked recessive disorders

• They are more “common” in __ (males/females)

• Only have 1 _ chromosome meaning favoring recessive disease presentation

Autosomal Dominant Pedigree

• Successive generations affected

• Males/females affected equally

• Transmitted to generations by males OR females

(Disorder pattern)

FBN1, pleiotropy, dominant

Marfan Syndrome

• Loss of function mutation in __ gene on chromosome 15q

• __ = genetic pattern

• Sx - Tall stature, stretchy extremities, aortic dissections

• Autosomal __ disorder

PMP22, dominant

Charcot-Marie-Tooth Type I

• Duplication of __ gene on chromosome 17q

• Cytotoxic duplication and promote apoptosis of peripheral NS → high arch of foot and limb deformities

• Autosomal __ disorder

Coloboma, Heart, Atresia, Retardation, Genital, Ear

CHARGE Syndrome - CHARGE

• __ (eye defect)

• __ defects

• __ of choanae (blocked nasal passages)

• __ (growth)

• __ underdevelopment (hypogonadism)

• __ abnormalities (ENT)

CHD7, dominant

CHARGE Syndrome

• Mutation in __ gene on chromosome 8q

• Autosomal __ disorder

Autosomal Recessive Pedigree

• Can skip generations

• Males/females affected equally

• Transmitted by healthy parents to affected offspring

• Higher with inter-mating

(Disorder pattern)

CFTR, Cl-, recessive

Cystic Fibrosis

• Loss of function mutation in __ gene on chromosome 7q

• Not able to export __ ion → sx - mucus buildup, lung infections, GI issues

• Autosomal __ disorder

HBB, pleiotropy, allelic, recessive

Sickle Cell Disease

• Point mutation to __ gene on chromosome 11p

• Sx - Crises with joint pain, fatigue, jaundice

• __tropy and __ heterogeneity = genetic pattern

• Autosomal __ disorder

COL1A1, COL1A2, locus, recessive

Osteogenesis Imperfecta I

• Mutation to __ (chromosome 17q)

• OR Mutation to __ (chromosome 7q)

• __ heterogeneity = genetic pattern

• Sx - Blue sclera of eye, hearing loss, brittle bones

• Autosomal __ disorder

BCKDHA, BCKDHB, DBT, recessive

Maple Syrup Urine Disease (MSUD)

• __ on chromosome 19q

• __ on chromosome 6q

• __ on chromosome 1p

• Sx - lethargy, weak sucking, poor feeding/weight gain, dark urine with odor

• Autosomal __ disorder

HEXA, recessive

Tay Sachs Disease

• Mutation in __ gene on chromosome 15q

• Sx - Motor/mental deterioration, loss of learned behaviors/milestones, cherry red dot to macula of eye

• Autosomal __ disorder

X-Linked Dominant Pedigree

• Affected fathers with non-affected mothers

• Non-affected sons and all daughters affected

• Affected mothers with non-affected fathers

• More females > males affected

(Disorder pattern)

MECP2, methylation, dominant

Rett Syndrome

• Mutation in __ gene on chromosome X1

• Sx - DNA __ in cells → Neurological deficits, apnea, hyperventilation, neuro-devastated

• X-linked __ disorder

X-Linked Recessive Pedigree

• Heterozygous females unaffected but can show mild sx

• Affected fathers pass mutation to all daughters

• More males > females affected

(Disorder pattern)

F8, bleeding, recessive

Hemophilia A

• Mutation in __ gene on chromosome Xq

• Sx - Excessive __ and prone to hemorrhaging

• X-linked __ disorder

DMD, recessive

Duchenne Muscular Dystrophy

• Mutation in __ gene on chromosome Xp

• Sx - Delayed motor skills, Gower maneuver (crane posture), cardiac abnormalities

• X-linked __ disorder

Opsin, X, males, recessive

Colorblindness

• Defects to several genes (i.e. __) located on _ (X/Y) chromosome

• Sx - Unable to see red-green color due to cone defects

• Affects __ (gender) more as X-linked __ disorder

Barr body

X chromosome that has been inactivated by dosage compensation

Pleiotropy

Many random phenotypes from single allele mutation

Allelic Heterogeneity

More than 1 point mutation in particular gene

Locus Heterogeneity

Single disease phenotype from mutation in different genes/loci

Marfan, Charcot-Marie-Tooth I, CHARGE

Autosomal Dominant Single-Gene Disorders - (3)

Cystic fibrosis, sickle cell, osteogenesis imperfecta, maple syrup urine, tay sachs

Autosomal Recessive Single-Gene Disorders - (5)

Hemophilia, Duchenne muscular dystrophy, colorblind

X-Linked Recessive Single-Gene Disorders - (3)